Feasibility, reproducibility and characteristics of coronary bifurcation type assessment by three-dimensional optical coherence tomography.

AIM: To investigate the characteristics of coronary artery bifurcation type (parallel or perpendicular type) using three-dimensional (3D) optical coherence tomography (OCT), and determine the feasibility, reproducibility, assessment time and correlation with bifurcation angles measured by 3D quantitative coronary angiography (QCA). METHODS AND
RESULTS: We evaluated 60 lesions at the coronary bifurcation that were treated by main vessel (MV) stenting with kissing balloon inflation (KBI) under OCT/optical frequency domain imaging (OFDI) guidance. Inter- and intra-observer agreement regarding the assessment of 3D bifurcation types were 0.88 and 0.94, respectively. The assessment times of 3D-OCT bifurcation type with OCT and OFDI were within about 30 seconds. 3D-OCT bifurcation types showed the greatest correlation with the distal bifurcation angle assessed by 3D-QCA among the three bifurcation angles (distal bifurcation angle, proximal bifurcation angle and main vessel angle), and the optimal cut-off distal bifurcation angle to predict a perpendicular type bifurcation, as determined by ROC analysis, was 51.0° (AUC 0.773, sensitivity 0.80, specificity 0.67). Based on this cut-off value for the distal bifurcation angle (51°), the diagnostic accuracy for perpendicular type bifurcation in cases with a BA ≥ 51° (n = 34) was 70.6% (24/34) and that of the parallel type bifurcation in cases of BA < 51° (n = 26) was 76.9% (20/26).
CONCLUSION: Performing 3D-OCT for assessment of coronary artery bifurcation type is feasible and simple, and can be done in a short time with high reproducibility.

Introduction

Coronary bifurcation lesions account for 15%– 20% of percutaneous coronary interventions (PCI) and remain one of the most challenging situations in interventional cardiology in terms of procedural success rates and long-term cardiac events [1]. Bifurcation angle (BA) is one of the factors related to clinical outcomes during and after treatment for bifurcation lesions [2-7]. Although BA can be measured by quantitative coronary angiography (QCA), the accuracy of BA derived from two-dimensional (2D) QCA is limited because of overlapping of branches and vessel foreshortening. Measuring BAs is theoretically more precise with three-dimensional (3D) rather than 2D-QCA [8, 9]. Recently, optical coherence tomography (OCT) has been used as a guide for treating bifurcation lesions [10, 11]. Three-dimensional reconstruction using OCT pullback facilitates understanding of interactions between stents and vessel walls [12]. Bifurcation type, whether perpendicular or parallel, as determined by 3D-OCT, was introduced as a parameter for visually assessing bifurcation appearance and was found to be associated with the incidence of incomplete stent apposition (ISA) at the side branch (SB) ostium after bifurcation PCI [13, 14]. However, the characteristics of bifurcation type on 3D-OCT are not well known. Therefore, we investigated the characteristics of 3D-OCT bifurcation type to determine its feasibility, reproducibility, assessment time and correlation with respect to the 3D-QCA bifurcation angle. In addition, the correlation between 3D-OCT bifurcation type and ISA at the bifurcation segment after single stenting with kissing balloon inflation (KBI) was also evaluated.

Methods

Study population

This study included all consecutive patients who underwent PCI for de-novo bifurcation lesions, which had a SB more than 2 mm in diameter by visual assessment, under OCT or Optical Frequency Domain Imaging (OFDI) guidance at Yamaguchi University Hospital between January 2013 and November 2017, using the strategy of a simple single stent crossing over a SB and subsequent KBI. The main exclusion criteria were in-stent restenosis, cardiogenic shock, chronic total occlusion, ST-elevation myocardial infarction and the bifurcation anatomy of trifurcation.

This retrospective study protocol was approved by The Medical Ethics Committee of Yamaguchi University Hospital. All patients had the opportunity to opt-out of the study.

Quantitative coronary angiography

BAs (distal BA, proximal BA, and main vessel (MV) angle), which were measured in the diastolic phase on 3D images generated from two pre-procedure coronary angiograms that were separated by > 30°, were measured by QAngio® XA 3D Research Edition, v1.0 software (Medis Specials, Leiden, the Netherlands) [8]. The distal BA was defined as the angle between the distal main branch and side branch, the proximal BA was defined as the angle between the proximal MV and SB, and the MV angle was defined as the angle between the proximal MV and distal main branch [8, 15]. Additionally, the reference lumen diameter, minimum lumen diameter of each branch, and percent diameter stenosis were analyzed using the QAngioXA version 7.3 (Medis Specials, Leiden, the Netherlands) [16].

Procedure and OCT image acquisition

We acquired OCT pullbacks using an Iluminen™ OCT Imaging system (Abbott Vascular, Santa Clara, CA, USA) with a Dragonfly™ intravascular imaging catheter (Abbott Vascular), or the Lunawave™ OFDI system (Terumo Corporation, Tokyo, Japan) with a FastView™ intravascular imaging catheter (Terumo Corporation). Automatic pullbacks proceeded at 18 or 36 mm/s for OCT and at 20 or 40 mm/s for OFDI during contrast injection for blood clearance from the lumen area using a power injector. The 3D-OCT/OFDI images acquired from all patients were reconstructed using an online system. Distal and proximal reference site and minimum lumen site were determined from longitudinal and cross-sectional OCT/OFDI images of MV pullback, and distal reference lumen area, proximal reference lumen area and minimum lumen area were analyzed.

Three-dimensional OCT/OFDI reconstruction and quantitative analysis

3D-OCT bifurcation types were assessed according to whether their bifurcations appeared parallel or perpendicular on pre-procedural 3D-OCT/OFDI images [13]. Briefly, the perpendicular type was defined as a bifurcation in which the SB opening was visible as an elliptical shape and was not concealed by the carina when viewed perpendicular to the vessel wall on the cut-away view of the 3D-OCT/OFDI image. In contrast, parallel type bifurcation was defined as a bifurcation in which the proximal course of the SB was concealed behind the carina [13] (Fig 1). The feasibility, reproducibility, and assessment time of 3D-OCT bifurcation type was also evaluated. To ensure inter-observer reproducibility of the assessment of 3D-OCT bifurcation type, thirty-four randomly selected images were assessed by a dedicated interpreter (T.N.) and an independent second interpreter (T.O.). Thirty-four images were assessed to ensure intra-observer reproducibility of the assessment of 3D-OCT bifurcation type at ≥ 4 weeks after the initial evaluation. Assessment time of the 3D-OCT bifurcation type was defined as the time from the start of 3D reconstruction on the OCT/OFDI console to completing the visual assessment of 3D-OCT bifurcation types. The relationship between 3D-OCT bifurcation type and the BA derived by 3D-QCA was also investigated.

Fig 1

Definition of 3D-OCT bifurcation type.

Parallel type: The proximal SB course is concealed behind the carina when viewed perpendicular to the vessel wall. Perpendicular type: The visible elliptical SB opening is not concealed by the carina when viewed perpendicular to the vessel wall. Blue arrows, direction of 3D image view. 3D, three-dimensional; SB, side branch, MV, main vessel.

Additionally, post-procedural OCT images were quantified. Frame-by-frame cross-sectional images were analyzed by counting all individual struts on each frame. ISA, including floating struts at the SB ostium, defined as separation of at least one stent strut from the vessel wall, was evaluated. Struts were classified as ISA if the distance between the strut marker and lumen contour exceeded the specific strut thickness plus axial resolution of OCT (14 μm) [17]. Strut apposition was assessed in every frame of the bifurcation segment [18]. All distances were measured in perpendicular cross-sections from OCT pullback in the MV. ISA struts at the bifurcation segment were counted. The incidence of ISA was assessed in terms of either the cut-off value of the distal bifurcation angle in 3D-QCA or the 3D-OCT bifurcation type.

Statistical analysis

Continuous data are presented as means ± standard deviation (SD) if normally distributed, or as medians and interquartile ranges (IQRs) if not. Continuous variables were compared using Student t-tests if normally distributed and the nonparametric Wilcoxon rank-sum test if not. Categorical variables are presented as numbers and ratios (%) determined in chi-squared tests. Inter- and intra-observer agreement regarding assessments of the 3D-OCT bifurcation type was determined using the kappa statistic. In addition, receiver operating characteristic curve analysis of the distal BA, proximal BA and MV angle was performed to identify the optimal cut-off value of the BAs for prediction of perpendicular type bifurcation. All data were statistically analyzed using JMP software (version 13, JMP Pro, SAS Institute Japan, Tokyo, Japan). All statistical tests were two-sided, and values with p < 0.05 were considered significant.

Results

The flow of patient selection in this study is shown in Fig 2. We initially assessed 68 bifurcation lesions in 67 consecutive patients based on the inclusion and exclusion criteria. In the assessment of 3D-OCT bifurcation type, 91.2% (62/68) of the lesions were assessable. In the six cases in which bifurcation type could not be assessed, assessment inability was due to artefacts of the guidewire shadow in four cases and non-uniform rotational distortion (NURD) in two cases. In the measurement of 3D-QCA BA, 97.1% (66/68) of the lesions were assessable. Two cases were not assessable due to difficulties in separating the MV from the SB. Finally, we analyzed 60 bifurcation lesions in 59 patients. Tables 1 and 2 summarize the characteristics of the patients, and characteristics of the lesions and procedures, respectively.

Fig 2

Study flow chart.

OCT, optical coherence tomography; OFDI, optical frequency domain imaging; PCI, percutaneous coronary intervention; SB, side branch; 3D, three-dimensional, QCA, quantitative coronary angiography.

Table 1

Patient characteristics.

Variable	n = 60
Age, mean ± SD	71.2 ± 7.9
Male sex, n (%)	46 (76.7)
Hypertension, n (%)	46 (76.7)
Dyslipidemia, n (%)	43 (71.7)
Diabetes mellitus, n (%)	27 (45.0)
Hemodialysis, n (%)	4 (6.7)
Former smoker, n (%)	37 (61.7)
Clinical presentation
Stable angina pectoris, n (%)	13 (21.6)
Unstable angina pectoris, n (%)	7 (11.7)
Old myocardial infarction, n (%)	3 (5.0)
Silent ischemia*, n (%)	37 (61.7)

SD = standard deviation,

*including staged PCI.

Table 2

Lesion and procedure characteristics.

Variable	n = 60
Treated bifurcation, n (%)
LM	34 (56.7)
LAD	16 (26.7)
LCx	6 (10.0)
RCA	4 (6.7)
Medina classification, n (%)
(1,1,1)	1 (1.7)
(1,1,0)	22 (36.7)
(1,0,0)	1 (1.7)
(0,1,1)	3 (5.0)
(0,1,0)	33 (55.0)
Stent type, n (%)
BMX-J	24 (40.0)
Resolute integrity	16 (26.7)
Ultimaster	9 (15.0)
Synergy (Promus Premier)	11 (18.3)
Stent size, mm	3.5 [2.5–3.5]
Stent length, mm	22.0 [18.0–25.5]
Kissing balloon inflation
MV balloon size, mm	3.0 [2.75–3.5]
SB balloon size, mm	2.5 [2.0–3.0]
Rotational atherectomy, n (%)	6 (10.0)
Pre-dilatation, n (%)	57 (95.0)
Post-dilatation, n (%)	59 (98.3)
POT, n (%)	34 (56.7)
Distal recrossing, n (%)	56 (93.3)
Pre-procedural QCA
Proximal main vessel
Ref. lumen diameter, mm	3.1 [2.55–3.7]
Min. lumen diameter, mm	2.5 [2.0–3.1]
% Diameter stenosis	15.1 [5.9–35.2]
Distal main vessel
Ref. lumen diameter, mm	2.0 [1.7–2.6]
Min. lumen diameter, mm	1.3 [0.8–1.9]
% Diameter stenosis	30.0 [21.0–56.4]
Side branch
Ref. lumen diameter, mm	2.4 [1.9–3.1]
Min. lumen diameter, mm	2.1 [1.6–2.7]
% Diameter stenosis	13.7 [8.4–21.5]
Pre-procedural OCT analysis
Proximal ref. lumen area, mm2	9.3 [6.6–12.7]
Distal ref. lumen area, mm2	5.3 [3.6–6.9]
Minimum lumen area, mm2	1.8 [1.2–2.6]
OCT/OFDI system, pullback speed
OCT, 18 mm/s	9 (15.0)
36 mm/s	25 (41.7)
OFDI, 20 mm/s	10 (16.7)
40 mm/s	16 (26.7)
Flushing material
Contrast	60 (100.0)

LM, left main; LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery; MV, main vessel; SB, side branch; POT, proximal optimization technique; QCA, quantitative coronary angiography; Ref, reference; Min, minimum; OCT, optical coherence tomography; OFDI, optical frequency domain imaging.

Assessment time and reproducibility of 3D-OCT bifurcation type

Assessment time of 3D-OCT bifurcation type in OCT and OFDI were 6.9 ± 1.5 seconds and 30.1 ± 4.2 seconds, respectively. Inter- and intra-observer agreement regarding the assessment of 3D-OCT bifurcation types were 0.88 and 0.94 in the kappa statistic, respectively.

Relationship between 3D-OCT bifurcation types and 3D-QCA BAs

Fig 3 shows the results of ROC curve analysis of the ability of the distal BA, proximal BA and MV angle to predict perpendicular type bifurcation. The optimal cut-off values of distal BA, proximal BA and MV angle to predict perpendicular type bifurcation on ROC analysis were 51.0° (AUC 0.773, sensitivity 0.80, specificity 0.67), 136.0° (AUC 0.726, sensitivity 0.50, specificity 0.90), and 137.0° (AUC 0.530, sensitivity 0.43, specificity 0.73), respectively. Therefore, the distal BA showed the greatest correlation with 3D-OCT bifurcation types among the three BAs. The cumulative curve for distal BAs is shown in Fig 4. Based on the cut-off value for the distal BA of 51°, the diagnostic accuracy for perpendicular type bifurcation in cases with a BA of ≥ 51° (n = 34) was 70.6% (24/34), and that for parallel type bifurcation in cases with a BA of < 51° (n = 26) was 76.9% (20/26). Moreover, the concordance rate of 3D-OCT bifurcation types was 61.5% (16/26) in identifying BAs close to the cut-off value (40–59°), whereas it was 82.4% (28/34) in cases outside this range of distal BA.

Fig 3

Receiver operating characteristic curve analysis to predict perpendicular type coronary bifurcation.

AUC, area under the curve; BA, bifurcation angle.

Fig 4

Cumulative curve analysis for the distal bifurcation angle.

The vertical dotted line indicates the cut-off angle of 51° for prediction of perpendicular type bifurcation. BA, bifurcation angle.

With respect to the incidence of ISA at the bifurcation segment, there were no significant differences between distal BAs of < 51° and distal BAs of ≥ 51° (6.1 [2.5–12.2] % vs. 9.1 [3.3–15.9] %, p = 0.30), while there was a significant difference between parallel and perpendicular types (4.3 [1.7–12.2] % vs. 10.0 [4.7–18.2] %, p = 0.014). Representative cases are shown in Fig 5.

Fig 5

Representative 3D-OCT bifurcation types.

Parallel type: Jailed stent struts at the SB ostium can be attached towards the SB wall by KBI in parallel type bifurcations in which the distal bifurcation angle is 50°. Perpendicular type: Jailed stent struts at the SB ostium cannot be sufficiently dilated to fit the elliptical SB ostial rim in perpendicular type bifurcations with a distal bifurcation angle of 106°. OCT, optical coherence tomography, SB, side branch, KBI, kissing balloon inflation, QCA, quantitative coronary angiography.

Discussion

The main findings of this study were as follows: 3D-OCT bifurcation type shows the greatest correlation with the distal BA measured by 3D-QCA. Assessment of the 3D-OCT bifurcation type is feasible and can be done visually and easily in a short time with high reproducibility.

Assessment of BA

BAs can be measured using various methods, including coronary computed tomography angiography (CCTA) and QCA. Previous publications reported that measurements by CCTA reflected real BAs in in vitro experiments [19, 20]. However, CCTA is not performed before the procedure in all cases. 3D-QCA requires dedicated bifurcation software. OCT can be used as a guide for stent optimization [21, 22]. Three-dimensional OCT/OFDI during PCI allowed simple and rapid visual assessment of the appearance of the bifurcation immediately after 3D reconstruction of bifurcation lesions, with high reproducibility. Although the assessment time in OFDI was longer than that when using the OCT system in the present study, it was acceptable during PCI [23].

Clinical significances of BA and 3D-OCT bifurcation type

Clinical significances of the coronary BA have been discussed in previous numerical reports. Because of the association between the 3D-OCT bifurcation type and the distal BA, the information of 3D-OCT bifurcation type (parallel or perpendicular) before stenting might help us to determine the treatment strategy in bifurcation lesions.

Watanabe et al. found a strong correlation between the carina-tip angle, which was defined as the angle between the MV lumen contour line and the SB lumen contour line at the carinal surface in OCT images, and the BA derived from CCTA [24]. Moreover, a narrower carina-tip angle (less than 50°) was an independent predictor of SB complications, defined as angiographic worsening of SB stenosis (>75%) after OCT-guided bifurcation stenting [25]. It is curious that our cut-off BA of 51° for discriminating between parallel and perpendicular type bifurcations was very similar to the narrower carina-tip angle for predicting SB compromise in this previous study.

Chen et al. reported that the 1-year MACE rate in the DK crush group was significantly lower than that in the Culotte group among patients with distal BA ≥ 70° [26], which was classified as the perpendicular type bifurcation. Moreover, it has been reported that a significant negative correlation was found between the uncovered strut percentage at the bifurcation segment and distal BA (r = -0.41, P = 0.0024) [24]. With respect to the ISA including the jailing struts at the bifurcation segment after KBI, the distal rewiring into the jailed SB could reduce ISA in the parallel type bifurcation whereas ISA was not always reduced by distal rewiring in the perpendicular type [14]. Besides ISA at the bifurcation segment, 3D-OCT bifurcation type might also be related to SB compromise and restenosis after PCI. Further investigations are warranted to confirm this.

Differences in the assessment of BA between 3D-QCA and 3D-OCT

The present study showed a discrepancy in the incidence of ISA at the bifurcation segment when using the cut-off value of the distal BA in 3D-QCA evaluation versus the 3D-OCT bifurcation type. We speculate that this phenomenon might be caused by vessel straightening due to the guidewire and by OCT/OFDI catheter insertion into the MV. In other words, 3D-OCT bifurcation type might reflect the relationship between the MV and SB takeoff after stent deployment, almost like predicting the appearance of vessel straightening after stent deployment in advance, because 3D-OCT images were obtained while keeping the vessel straight. In contrast, we hypothesized that 3D-QCA reflects the natural coronary BA. Therefore, 3D-OCT bifurcation type rather than BA on 3D-QCA might better reflect the BA after stent deployment into the MV, and might be associated with ISA at the bifurcation segment after final KBI. Further studies are warranted to confirm these theories.

Limitations

This study has some limitations. First, this study only included patients who were treated by single stenting with KBI, and bifurcation lesions that were left untreated or were treated by other techniques were not evaluated in this study. This might have influenced the cut-off angle used to predict perpendicular type bifurcations. However, in a clinical setting, assessment of the BA is needed for PCI. Second, we compared 3D-OCT with 3D-QCA, which is more accurate than 2D-QCA. However, BA measured by 3D-QCA might be different from the actual BA. Moreover, this study included both OCT and OFDI. We did not compare these two different assessment systems. Use of IVUS and OCT is recommended for stent optimization during the bifurcation stenting in the current guideline [27]. IVUS also might predict the side branch complication and the bifurcation angle. The previous report showed that the ‘‘eyebrow” sign associated with narrower angiographic angles was a powerful predictor of the SB damage after stent implantation in the MV [28]. Further study to investigate the superiority between both modalities may be warranted. Finally, we did not investigate other clinical implications of 3D-OCT bifurcation type (i.e., prediction of SB compromise, clinical outcomes, etc.) except for ISA at the bifurcation segment after KBI, and we did not compare the ISA at bifurcation between the parallel type and the perpendicular type due to difficulties adjusting many confounders (S1 Table). Further studies are needed to address this.

Conclusions

Visual assessment of 3D-OCT bifurcation type is feasible and can be easily performed in a short time with high reproducibility. Moreover, it correlates well with the BA measured by 3D-QCA and might be useful to assess BA during PCI.

Supplementary table.

SD = standard deviation, *including staged PCI, LM, left main; LAD, left anterior descending; LCx, left circumflex; RCA, right coronary artery; MV, main vessel; SB, side branch; POT, proximal optimization technique; QCA, quantitative coronary angiography; Ref, reference; Min, minimum; OCT, optical coherence tomography.

(DOCX)

Click here for additional data file.

Analysis data.

(XLSX)

Click here for additional data file.

4 Oct 2021

PONE-D-21-25048

Feasibility, reproducibility and characteristics of coronary bifurcation type assessment by three-dimensional optical coherence tomography

PLOS ONE

Dear Dr. Okamura,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please respond the problems pointed out by reviewers.

Please submit your revised manuscript by Nov 18 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see:  http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at  https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Yoshiaki Taniyama, MD, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

2. Please provide additional details regarding participant consent. In the Methods section, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

3. Please be informed that Dr. Okamura received honoraria from Terumo corp and Abbott vascular. The other authors have no conflict of interest to declare with the manuscript from the cover letter. This information should be added to the COI.

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors reported the feasibility and reproducibility of online visual 3D-OCT assessment of bifurcation lesion . 3D-OCT bifurcation type is tentatively correlated with the distal bifurcation angle measured by 3D-QCA. This manuscript is well written and organized. However, following issues need to be addressed.

1. It is unclear what will be the clinical implication of the bifurcation type. Debate persists regarding the optimal treatment of side branch bifurcation lesions including assessment of clinical significance. How can the information of bifurcation type before stenting help us to determine the treatment strategy in bifurcation lesion? Basically, it is not a valuable publication unless the authors demonstrate the clinical implication of this study. Please discuss about that.

2. The authors showed a correlation with the distal bifurcation angle measured by 3D-QCA. However, the clinical impact on bifurcation angle before stenting is limited. I believe that it is more important to acquire optimal projection detected by coronary CT or functional assessment using FFR/FFRCT/QFR than the recognition of bifurcation angle or type before procedure.

3. The authors did not describe the difference in lesion characteristic between parallel type and perpendicular. Is there any differences in lesion characteristics such as distal recrossing or appropriate POT or KBI which is the predictor of side branch complication? Please clarify this.

Reviewer #2: The manuscript entitled “Feasibility, reproducibility and characteristics of coronary bifurcation type assessment by three-dimensional optical coherence tomography” investigates the possible role of 3D-OCT to assess bifurcation angles as compared to 3D-QCA.

The manuscript is overall well written and the topic is interesting. Please find below my comments to improve the manuscript quality:

1) According to authors data, 3D OCT seems to be reliable for the detection of parallel and perpendicular bifurcation angles (BA). However, a binary classification of bifurcation angles into two types only might be poorly accurate and 3D OCT might be not accurate in identifying less overt angles (e.g 40-60°). It would be advisable to discuss this point or to include it in the limitations paragraph.

2) Authors justify the use of 3D OCT for the BA as 3d OCT represents also a useful tool for stent optimization. However, in several centres also IVUS is used for this purpose. Please discuss the possible role of IVUS in such context.

3) As reported by the authors, 51° is the cut-off for side branch complications. It would be interesting to add any possible complications in the parallel and perpendicular BAs, as well as in those with angles > and <51°.

4) Although the readership might be familiar with the topic, it would useful to add a figure explaining the three different BAs (distal, proximal and main vessel).

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Giulio Russo

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

17 Nov 2021

We thank the reviewers for carefully reading for our manuscript and for the reviewers’ comments, which have helped us to further improve the quality of our manuscript. We responded to the reviewers’ comments in ‘’Response to Reviewers’’ file. Please confirm the attached document.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

17 Jan 2022

Feasibility, reproducibility and characteristics of coronary bifurcation type assessment by three-dimensional optical coherence tomography

PONE-D-21-25048R1

Dear Dr. Okamura,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Yoshiaki Taniyama, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The author responded the problems.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: All issues raised during the revision process have been properly addressed and the manuscript is now suitable for publication

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Giulio Russo

21 Jan 2022

PONE-D-21-25048R1

Feasibility, reproducibility and characteristics of coronary bifurcation type assessment by three-dimensional optical coherence tomography

Dear Dr. Okamura:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Yoshiaki Taniyama

Academic Editor

PLOS ONE