Tip Detection–Antegrade Dissection and Re-Entry With New Puncture Wire in CTO Intervention

Background The authors devised the tip detection (TD) method and developed AnteOwl WR intravascular ultrasound to standardize intravascular ultrasound–based 3-dimensional wiring for intraplaque tracking in chronic total occlusion (CTO)–percutaneous coronary intervention (PCI). The TD method also allowed antegrade dissection and re-entry (ADR). Combining TD-ADR with Conquest Pro 12 Sharpened Tip (CP12ST) wire, a new ADR wire with the strongest penetration force developed to date, enabled re-entry anywhere except calcification sites. Objectives This study investigated the efficacy and feasibility of TD-ADR by comparison of procedural outcomes with Stingray-ADR in CTO-PCI. Methods Twenty-seven consecutive CTO cases treated by TD-ADR with CP12ST wire between August 2021 and April 2023 and 27 consecutive CTO cases treated by Stingray-ADR with Conquest 8-20 (CP20) wire between March 2018 and July 2021 were retrospectively enrolled as the TD-ADR by CP12ST wire group and Stingray-ADR by CP20 wire group, respectively, from 4 facilities that could share technical information on these procedures. Results The success rate of the ADR procedure was significantly improved (27 of 27 cases [100%] vs 18 of 27 cases [67%], respectively; P = 0.002) and total procedural time was significantly reduced (median procedural time: 145.0 [Q1-Q3: 118.0-240.0] minutes vs 185.0 [Q1-Q3: 159.5-248.0] minutes, respectively; P = 0.028) in the TD-ADR by CP12ST wire group compared to the Stingray-ADR by CP20 wire group. There were few in-hospital major adverse cardiac and cerebrovascular events or no complications in either group. Conclusions TD-ADR by CP12ST wire can standardize highly accurate ADR in CTO-PCI.

I n chronic total occlusion (CTO)-percuta- neous coronary intervention (PCI), if guidewires cannot be passed through the CTO lesion in angiography-based antegrade wire escalation, it is recommended to move on to the retrograde approach 1 or antegrade dissection and re-entry (ADR) using the Stingray system (current device-based ADR, Boston Scientific). 2 These 2 strategies are effective, but have some problems.The retrograde approach uses a donor artery, which is a complex procedure and has a high risk of complications. 3 Current devicebased ADR has been widely used, but it does not have a high level of accuracy because this procedure uses angiographic observation. 2There is a lack of standardized accurate anterograde wiring techniques that should be performed before applying these 2 strategies.
To standardize the accurate anterograde wiring technique in CTO-PCI, over the last 13 years we have developed various methodologies and devices based on the 3-dimensional (3D) wiring method (Figure 1).
Until recently, IVUS-guided wiring had been thought to be "intraplaque tracking" through the intraplaque route but not "re-entry" from the subintimal space to the true lumen.Therefore, we attempted to pass through the intraplaque route using the TD method (Figure 1B).However, in November 2021, we found that the TD method allows ADR because the wall between the subintima and the true lumen can be punctured at the intended site in an exactly vertical direction under IVUS observation. 12 named this method "tip detection-ADR" (TD-ADR) (Figure 1C). 13Compared with current devicebased ADR, TD-ADR enables puncture at a more INTERVENTIONAL PROCEDURES UNTIL ADR IN CTO-PCI.A 7-or 8-F guide catheter was selected for the antegrade approach at the discretion of the operator.In antegrade wire escalation, the tip of the CTO stiff wires was 1 mm with a curve at an angle of 45 .A Corsair microcatheter (Asahi Intecc Co, Ltd) was mainly used because of sufficient backup support for the CTO guidewires.When the antegrade guidewire was advanced to be around the CTO exit but could not be passed through the CTO lesion due to advancement of the guidewire into the subintimal space, or intraplaque area other than the distal lumen, we changed to Stingray-ADR, IVUS-guided wiring, or the retrograde approach, while following the CTO-PCI algorithms. 16,17TERVENTIONAL PROCEDURES OF CURRENT DEVICE-BASED ADR IN CTO-PCI.In current devicebased ADR, we followed the Japanese ADR technique advocated by Habara et al. 18 Briefly, the stick-and-swap technique was attempted in all cases using the Stingray system with CP20 wire for stick and XT-R (Asahi Intecc Co, Ltd) for swap under angiographic guidance (Central Illustration A).After March 2018, when the Stingray balloon was delivered and inflated at the target position, aspiration was performed for 4 minutes using the guidewire lumen of the Stingray balloon to reduce the hematoma.

INTERVENTIONAL PROCEDURES OF TD-ADR IN
CTO-PCI.In TD-ADR, when the first antegrade guidewire was advanced to be around the CTO exit but could not be passed through the CTO lesion due to advancement of the guidewire into the subintimal space, or intraplaque area other than the distal lumen, (Figure 2A), the Corsair was advanced through the guidewire around the CTO exit to create a space for the IVUS catheter (Figures 2B and 2C).If the guidewire was a tapered wire, it was changed to a Tanaka et al 0.014-inch moderately stiff CTO wire to obtain good support for advancing the IVUS catheter.Using a double-chamber catheter, the second guidewire was then advanced and the microcatheter was advanced through this second wire, and the IVUS catheter was advanced through the first guidewire (Figure 2D).In addition, when the IVUS catheter could not be advanced after the Corsair's bougie, balloon dilatation was performed with a small-diameter balloon.
We used AO-IVUS in all cases of IVUS-guided wiring.First, we discuss how to recognize the location of the target (intraplaque, exit lumen of the CTO, etc), which can be visualized by IVUS, on the angiographic image.We also used the TD method, as shown in   the advancement of the guidewire tip.In TD-ADR, the above-mentioned IVUS observation using TD method was also performed, and the wall between the subintima and the true lumen was punctured at the intended site in an exactly vertical direction.
We attempted to create the re-entry just beyond the CTO exit.However, if puncture was difficult, we changed to puncture at the distal part.In September 2022, we found that TD-ADR at the CTO body was also possible. 15Since then, we have performed puncture at the CTO body when attempting to shorten the length of subintimal passage or when the CTO exit was located at the bifurcation site.
Since the approval of CP12ST wire in August 2021, CP12ST wire has been used in all TD-ADR cases.
Details of the TD-ADR procedure follow (Figure 4). 2. Fixing the guidewire shaft in the subintimal space (Figure 4C): Unlike TD-intraplaque tracking, it is difficult to fix the guidewire in the subintimal space.Therefore, in addition to forming an adequate second curve (step 1), it is necessary to consider the position and rotational direction of the guidewire for the shaft to be fixed against the IVUS catheter or vessel wall during puncture.4D): The wall is punctured at the intended site in a vertical direction on the short-axis view of the IVUS image.In addition, a vertical puncture on the long-axis view can be recognized to some extent through fluoroscopy.4E and 4F): Once the tip has penetrated the wall, it is advanced about 5 mm while keeping the apex of the tip inside the distal lumen.

Swap (Figures
Then, the microcatheter is advanced into the lumen, and the tip of the microcatheter can be detected by the acoustic shadow under IVUS observation.The puncture guidewire is then changed to a soft guidewire.In addition, if it is difficult to pass the microcatheter after a successful puncture with the guidewire, consider using the side branch balloon anchor method or the GP-Lock method. 19CTO was defined as a totally occluded lesion with an estimated duration of at least 3 months with TIMI flow grade 0. The J-CTO (multicenter CTO registry of Japan) score was applied as reported previously. 20e angiographic classifications, such as collateral connection grade, CTO entry type, calcification, bending, and lesion length, were defined as reported previously. 21A definition of a retrograde approach was any attempt to advance a wire through a retro-

RESULTS
DEMOGRAPHIC AND ANGIOGRAPHIC CHARACTER-ISTICS.Table 1 presents a summary of patient and lesion characteristics.There were no significant differences in the demographic or angiographic characteristics between the 2 groups.

COMPARISON OF PROCEDURAL OUTCOMES BETWEEN
STINGRAY-ADR AND TD-ADR.Figure 5 shows flow diagrams of the procedures in the 2 groups.In the Stingray-ADR by CP20 wire group, Stingray-based ADR was performed in all the 27 cases just after the primary antegrade wire escalation.Stingray-based ADR was successful in 18 cases; however, 9 cases required other methods, mainly TD methods, and only 1 case was unsuccessful.In the TD-ADR by CP12ST wire group, TD-ADR was performed in 13 cases just after the primary antegrade wire escalation.However, TD-ADR was performed after TDintraplaque tracking in 12 cases, and TD-ADR was performed after the retrograde approach in 2 cases, and TD-ADR was successful in all cases.was performed in all the 27 cases just after 13 the primary antegrade wire escalation.Stingray-based ADR was successful in 18 cases; however, 9 cases required other methods, and only 1 case was unsuccessful.(B) TD-ADR was performed in 13 cases just after the primary antegrade wire escalation.However, TD-ADR was performed after TD-intraplaque tracking or the retrograde approach in 14 cases, and TD-ADR was successful in all cases.Abbreviations as in Figures 1 and 4. in which the CTO body was successfully punctured in the TD-ADR by CP12ST wire group.There were no significant differences in the in-hospital major adverse cardiac and cerebrovascular events or complication rates between the 2 groups (Table 3).

REPRESENTATIVE CASES OF TD-ADT BY CP12ST
WIRE.A 54-year-old man with effort angina pectoris due to a CTO lesion in the left circumflex coronary artery was treated using TD-ADR by CP12ST wire (Figure 6A).After insertion of an 8-F guide, an XT-R wire could be advanced into the CTO lesion (Figure 6B).However, AO-IVUS observation revealed that it entered the subintima 1 cm beyond the CTO  True lumen cross-sectional area at the punctured site, mm 2 Ratio of the true lumen area to the vessel area at the punctured site 0.
entrance due to severe calcification (Figure 7A), whereas there was a true lumen without calcification 5 mm beyond the transition site.The true lumen could not be visualized angiographically, so we selected AO-IVUS-based TD-ADR by CP12ST wire instead of Stingray-based ADR.The CP12ST wire supported by a Corsair microcatheter was advanced to the re-entry site where we attempted re-entry (Figure 6C).The TD method allowed the tip of the CP12ST wire to puncture the wall of the true lumen in an exactly vertical direction, resulting in successful re-entry even though the true lumen had collapsed and had thick plaque (Figures 7C and 7D).After advancing the Corsair microcatheter into the true lumen, CP12ST wire was changed to a soft guidewire, which was advanced into the distal part (Figure 7D, Video 1).Normal antegrade blood flow was achieved after stent implantation (Figure 6D).In general, the current device-based ADR is not recommended in situations where the distal lumen cannot be visualized by contrast medium, the CTO exit is located at a bifurcation lesion, the plaque at the puncture site is thick, and the true lumen is collapsed or small. 2,18However, TD-ADR by CP12ST wire overcomes all of these situations because IVUS allows visualization of all the true lumen, re-entry from the CTO body is possible, the CP12ST wire has high penetration force, the TD method allows puncture regardless of the target size, and the Seldinger method 22 under IVUS observation makes it possible to accurately insert the tip of the microcatheter into the true lumen.That is, combining TD-ADR with CP12ST wire makes re-entry possible from anywhere regardless of the wall thickness except at sites of calcification.The disadvantage of TD-ADR is that the current  the ADR rate clearly increased, with a TD-ADR rate of 27 of 187 (14.4%) and a Stingray-based ADR rate of 27 of 317 (8.5%).This suggests that a paradigm shift has occurred in the strategy of CTO-PCI.As shown in the present study, the IVUS-guided TD method, TDintraplaque tracking [7][8][9][10] and TD-ADR, 12,13,15 is a highly accurate guidewire navigation technique, and we hope that the CTO-PCI algorithms will be changed in the future. 11In antegrade wire escalation, when the guidewires cannot pass through the CTO exit due to advancement into the subintimal space, or intraplaque area other than the distal lumen, the retrograde approach will be selected if there are promising interventional retrograde channels.However, in more situations than before, AO-IVUS will be inserted into the CTO lesions, followed by TDintraplaque tracking and TD-ADR.The retrograde approach is still necessary when the guidewires cannot be advanced into the CTO lesion or, although we have never experienced it, when the lesions are completely calcified and puncture sites cannot be found by IVUS observation.
In order to perform the TD method including TD-ADR, a short-tip pull back IVUS such as AO-IVUS is necessary, although additional medical expenses are required.We hope that AO-IVUS and CP12ST wire will also become available outside of Japan and the TD method will be widely adopted around the world.ADDRESS FOR CORRESPONDENCE: Dr Atsunori Okamura, Cardiovascular Center, Sakurabashi Watanabe Hospital, 2-4-32 Umeda, Kita-ku, Osaka 530-0001, Japan.E-mail: a_okamura@watanabe-hsp.or.jp.@Aokamura5.

FIGURE 2
FIGURE 2 Procedural Flow Up to IVUS-Guided Wiring

Figure 3 .
Figure 3.It is difficult to recognize the location of the target, such as the exit lumen of the CTO, which can be visualized by IVUS, on the angiographic images (Figure 3A).The second guidewire was advanced 1 cm before the transitional site of intraplaque area and subintimal space.On the angiographic image, the apex of the tip of the second guidewire faced the right (Figure 3B-a) and was rotated clockwise to place the apex of the tip directly facing the operator (Figures 3B-a and 3B-b).The TD method was then

First, we attempted
to pass the guidewire through the intraplaque routes by the TD method (TD-intraplaque tracking), and if difficult, changed to TD-ADR to pass the guidewire through the reentry route (Central Illustration B).During guidewire navigation, the tip and its direction were always visualized by moving the IVUS transducer back and forth at the guidewire tip part by an experienced second operator to visually construct the 3D image of the guidewire inside the vessel.In TD-intraplaque tracking, the guidewire tip was accurately guided to the target through the intraplaque route under direct visualization, whereas the transducer was always advanced in accordance with

FIGURE 3
FIGURE 3 Transfer of Positional Information From IVUS Images to Fluoroscopic Images Similar to Stingray-based ADR, TD-ADR uses the stick-and-swap technique, but based on IVUS guidance rather than angiographic guidance.1. Formation of an adequate second curve (Figures 4A and 4B): The puncture guidewire is advanced through the microcatheter, and how the apex of the guidewire tip can hit the wall is checked by IVUS observation.From the IVUS information, an additional second curve can be adequately formed, if necessary, such that the apex of the guidewire tip can hit the wall vertically on the short-axis view of the IVUS image.

FIGURE 4
FIGURE 4 Creation of the Re-Entry Under IVUS Observation in TD-ADR Tanaka et al STUDY DEFINITION INCLUDING IVUS ANALYSIS.
grade channel.Procedural success was defined as when both the guidewire and balloon crossed the occluded lesion completely, successfully dilating the occluded artery, and achieving restoration of antegrade flow (TIMI flow grade 3) with <50% residual stenosis on final angiography.Significant side branch occlusion beyond the CTO lesion was defined as occlusion of a side branch with a vessel diameter of 1.5 mm or more by angiography.In-hospital major adverse cardiac and cerebrovascular events consisted of cardiac and noncardiac death, Q-wave myocardial infarction, non-Q-wave myocardial infarction, target vessel failure followed by emergent target vessel revascularization with PCI or coronary artery bypass graft, and stroke.Myocardial infarction was defined as an increase in creatine kinase level to more than twice the upper limit of normal.Complications during the procedure consisted of vessel perforations recognized by the extravasation of contrast media by the guidewire without tamponade at the CTO site and vessel perforations leading to cardiac tamponade.The procedural time for Stingray-based ADR was the time from delivering the Stingray balloon into the lesion until successful re-entry and advancement of the guidewire into the distal lumen.The procedural time for TD-ADR was the time from delivering the AO-IVUS into the lesion until successful re-entry and advancement of the guidewire into the distal lumen.The IVUS data were sent to Sakurabashi Watanabe Hospital and were analyzed by an independent experienced IVUS data analyst.The wall thickness at the successfully punctured site was measured by IVUS.When the CTO body was punctured, the farthest distance that the guidewire tip reached from the puncture site during puncture was defined as the wall thickness that could be punctured.The true lumen cross-sectional area was measured and the ratio of the true lumen area to the vessel area was calculated as the true lumen cross-sectional area divided by the external elastic membrane crosssectional area at the successfully punctured site.The length of subintimal passage beyond the CTO exit was the distance from the CTO exit site to the reentered distal lumen site measured under IVUS observation.However, in the case of re-entry from the CTO body in TD-ADR, the length of subintimal passage was defined as 0 mm.STATISTICAL ANALYSIS.Continuous data were evaluated using the quantile-quantile plot and Kolmogorov-Smirnov test to check normality of continuous measures.Continuous data are expressed as the mean AE SD or median (Q1-Q3), whereas categorical values are expressed as percentages.Continuous data were compared using the unpaired Student's t-test (for normally distributed data) or the Mann-Whitney U test (for non-normally distributed data).Frequency functions were assessed using Fisher exact test and the chi-square test.In all analyses, P < 0.05 was taken to indicate statistical significance.All statistical analyses were performed using EZR software (version 1.61, Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R (R Foundation for Statistical Computing).

Table 2
presents the procedural outcomes.The total procedure time was significantly shorter in the TD-ADR by CP12ST wire group than in the Stingray-ADR by CP20 wire group (median: 145.0 [Q1-Q3: 118.0-240.0]minutes vs 185.0 [Q1-Q3: 159.5-248.0]minutes, respectively; P ¼ 0.028).Radiation absorbed dose and amount of contrast medium were also significantly reduced in the TD-ADR by CP12ST wire group compared with the Stingray-ADR by CP20 wire group.ADR-related procedural data were significantly improved in the TD-ADR by CP12ST wire group

FIGURE 5 Flow
FIGURE 5 Flow Diagram of Stingray-ADR by CP20 Wire and TD-ADR by CP12ST Wire

FIGURE 6
FIGURE 6 Angiographic and IVUS Images During the Procedures

FIGURE 7
FIGURE 7 IVUS Images During TD-ADR and Corresponding Illustrations STUDY LIMITATIONS.TD-ADR requires several techniques specific to this procedure and an assistant who can perform appropriate IVUS operations as a second operator.Stingray-based ADR was performed by CP12 wire but TD-ADR was performed by CP12ST wire.Therefore, a comparative study of Stingray-ADR by CP12ST wire and TD-ADR by CP12ST wire is necessary to determine whether TD-ADR is effective against Stingray-based ADR.The present study was based on retrospective data analysis of a relatively small number of patients (Comparison between number of cases <50).Further, multicenter and prospective randomized studies are needed to evaluate whether the TD-ADR by CP12ST wire method is effective and feasible for use in daily clinical practice.

FIGURE 8
FIGURE 8 IVUS Images During TD-ADR for 4 Other Impressive Cases .
Tanaka et alJ A C C : A S I A , V O L . 4 , N O . 5 , 2 0 2 4 Tip Detection-ADR by CP12ST Wire in CTO-PCI CONCLUSIONS TD-ADR by CP12ST might be an innovative method to standardize highly accurate ADR in CTO-PCI.ACKNOWLEDGMENT The authors thank Dr Yasushi Sakata (Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan) for advice on the organization of the present study.FUNDING SUPPORT AND AUTHOR DISCLOSURESDr Okamura has received speaker fees from Terumo Corp. Dr Tsuchikane has received consulting fees from Asahi Intecc, Boston Scientific, and Kaneka.All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

TABLE 2
Procedural Characteristics and Outcomes

TABLE 3
In-Hospital MACCE and Complications During the Procedure