Author + information
- Received December 23, 2016
- Revision received June 11, 2017
- Accepted June 15, 2017
- Published online November 6, 2017.
- Yoriyasu Suzuki, MDa,
- Etsuo Tsuchikane, MD, PhDb,∗ (, )
- Osamu Katoh, MDc,
- Toshiya Muramatsu, MDd,
- Makoto Muto, MDe,
- Koichi Kishi, MDf,
- Yuji Hamazaki, MDg,
- Yuji Oikawa, MDh,
- Tomohiro Kawasaki, MDi and
- Atsunori Okamura, MDj
- aDivision of Cardiovascular Medicine, Nagoya Heart Center, Aichi, Japan
- bDepartment of Cardiology, Toyohashi Heart Center, Aichi, Japan
- cJapanese CTO-PCI Expert Foundation, Okayama, Japan
- dDepartment of Cardiology, Tokyo General Hospital, Tokyo, Japan
- eDivision of Cardiology, Saitama Prefecture Cardiovascular and Respiratory Center, Saitama, Japan
- fDepartment of Cardiology, Tokushima Red Cross Hospital, Tokushima, Japan
- gDivision of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- hDepartment of Cardiovascular Medicine, The Cardiovascular Institute, Tokyo, Japan
- iDepartment of Cardiology, Shin-Koga Hospital, Fukuoka, Japan
- jDivision of Cardiology, Sakurabashi-Watanabe Hospital, Osaka, Japan
- ↵∗Address for correspondence:
Dr. Etsuo Tsuchikane, Department of Cardiology, Toyohashi Heart Center, 21-1 Gobutori Oyama-cho Toyohashi, Aichi, Japan 441-8530.
Objectives This report describes the registry and presents an initial analysis of outcomes for the different PCI approaches taken by the specialists.
Background Strategies for percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) are complex. The Japanese Board of CTO Interventional Specialists has developed a prospective, nonrandomized registry of patients undergoing CTO-PCIs performed by 41 highly experienced Japanese specialists.
Methods Over the study period of January 2014 to December 2015, the registry included 2,846 consecutive CTO-PCI cases undertaken in Japan. The authors compared clinical outcomes between the different PCI approaches, following the intention-to-treat principle.
Results The overall technical success rate of the procedures was 89.9%. The specialists frequently chose a retrograde approach as the primary CTO-PCI strategy (in 27.8% of cases). The technical success rate of the primary antegrade approach was significantly better than that of the primary retrograde approach (91.0% vs. 87.3%; p < 0.0001). The technical success rate decreased to 78.0% with the rescue retrograde approach. Parallel guidewire crossing and intravascular ultrasound–guided wire crossing were performed after guidewire escalation during antegrade CTO-PCI with a high technical success rate (75.0% to 88.9%). Severe lesion calcification was a strong predictor of failed CTO-PCI.
Conclusions CTO-PCI performed by highly experienced specialists achieved a high technical success rate.
Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is a well-accepted revascularization procedure that accounts for around 10% of PCI procedures. The initial success rate is increasing because of improvements in technology and techniques (1–7).
The current procedure for CTO-PCIs involves placing 2 guide catheters to facilitate a seamless transition between the antegrade wire-based, antegrade dissection re-entry-based, and retrograde (wire or dissection re-entry) techniques, the so-called “hybrid” interventional strategy (8–11). Thus, CTO-PCI strategies are highly complex and pre-procedural planning is important, as was described in the 2012 consensus document from the EuroCTO Club (12). Recently, some studies limited to the retrograde approach such as the Retrograde Summit registry have been reported from Japan (13,14). However, there are still few studies to evaluate CTO strategies. Because the skill level of the operators strongly influences the success of CTO-PCIs, results of CTO-PCI strategies by highly skilled operators should be important to assess CTO-PCIs.
To evaluate CTO-PCI strategies, the Japanese Board of CTO Interventional Specialists has developed a registry of Japanese CTO-PCI cases undertaken by highly experienced specialists. In this report, we describe the registry and present an initial investigation of clinical outcomes using “intention-to-treat” (ITT) analysis (15,16).
The CTO-PCI expert registry
The Japanese Board of CTO Interventional Specialists was established in July 2013. Initially, 30 highly experienced physicians were certified in 2013. This board certified a total of 41 physicians by the end of 2015. The board arranged for the development of a prospective, nonrandomized registry of patients undergoing CTO-PCIs performed by these 41 highly experienced Japanese specialists who had been certified by the board for this registry. The requirements for certification were that the specialist performed more than 50 CTO-PCIs per year and that they had performed more than 300 CTO-PCIs in total (12). The certified specialists are required to enroll all consecutive CTO-PCI cases into the registry, including cases undertaken abroad. The planned patient enrollment period is from January 2014 to December 2022, and clinical follow-up will continue until December 2027. Written informed consent is obtained from all patients in accordance with the protocol for this registry.
Short-term and long-term primary and secondary endpoints have been defined for the registry. The primary short-term endpoint is the technical success of all the CTO-PCI cases, and the secondary short-term endpoints are as follows: the number of in-hospital major adverse cardiac and cerebrovascular events (MACCEs) after CTO-PCIs (death, myocardial infarction, stroke, and revascularization during the same admission); an evaluation of the procedure time, irradiation time, contrast volumes, and the incidences of contrast-induced nephropathy; and the incidence of irradiation skin injury after CTO-PCIs for the interventions performed in Japan. The long-term primary and secondary endpoints (MACCEs and target vessel revascularizations, respectively) are evaluated after CTO-PCIs every year until 5 years.
All clinical data, including patient background data and details of the procedures, are input via an electronic capture system provided by the Japanese Board of CTO Interventional Specialists. The data are managed by the secretariat of the registry (Clinical Research Center, Kurashiki Central Hospital, Ohara Healthcare Foundation, Okayama, Japan), who would also perform the analyses of clinical data. Diagnostic coronary angiograms, computed tomography images of coronary arteries before the interventions, and coronary angiograms and intravascular ultrasound (IVUS) images obtained during interventions are sent as DICOM data to an independent core laboratory (Cardiovascular Imaging Center, Aichi, Japan) for further analysis. This laboratory assesses all coronary angiograms to centralize the appropriate assessment of the target CTO lesions, the morphologies of the target CTO lesions, and the CTO-PCI procedure outcomes.
Evaluation of outcomes
The present analysis evaluated the initial outcomes of CTO-PCI cases performed in 2014 and 2015, comparing the CTO-PCI strategies adopted by the specialists. The CTO-PCI procedure was defined here as the retrograde approach where an attempt was made to cross the collateral channel supplying the vessel distal to the target CTO lesion for retrograde revascularization techniques (17). The cases were divided into 3 groups according to the approach taken during the intervention: primary antegrade approach (PAA), primary retrograde approach (PRA), and rescue retrograde approach (RRA). The PAA group included procedures where the initial plan was to cross the CTO lesion antegradely, including cases where the antegrade approach failed and the procedure was switched to a retrograde approach. The PRA group included procedures initially planned to cross the CTO lesion using a retrograde approach. This group included cases where the retrograde approach failed and the procedure was switched to the antegrade approach. The RRA group included the PAA cases where the procedure was switched to a retrograde approach after the initially planned antegrade approach failed.
CTO was defined as the presence of Thrombolysis In Myocardial Infarction flow grade 0 within an occluded arterial segment for more than 3 months. Collateral connection grade was classified as previously reported (18). The J-CTO (Multicenter CTO Registry in Japan) score was used to classify lesion difficulty as previously reported (19). The angiographic classifications were defined as previously reported (20). In-hospital MACCEs were defined as death, myocardial infarction, stroke, and revascularization during the same admission. Contrast-induced nephropathy is defined as either a 25% increase in serum creatinine from baseline or a 0.5 mg/dl increase in absolute serum creatinine value within 72 h after CTO-PCIs (21,22).
Guidewire success, technical success, and procedural success were defined as previously described (20).
Comparisons between the PAA and PRA groups followed the ITT principle. Continuous data are presented as mean ± SD, and differences were compared using the Student t test and nonparametric methods. Discrete variables are expressed as counts and percentages. These were assessed using the Fisher exact test and the chi-square test, depending on the table size. A regression model was applied to identify the prognostic factors. A univariate regression analysis was performed to obtain the odds ratio for the possible predictors of failed CTO-PCIs in the overall, PAA, and PRA groups. Thereafter, a multivariate analysis was performed using the variables with p values <0.05 in the univariate analysis in order to examine the independent associations of failed CTO-PCIs in the overall, PAA, and PRA groups. In all analyses, p < 0.05 was considered to indicate statistical significance. Statistical analysis was performed using SPSS version 23 (IBM, Armonk, New York).
A flowchart of this study is shown in Figure 1. From January 2014 to December 2015, the 41 certified specialists performed 4,205 CTO-PCIs in Japan and other countries. Also, 1,359 cases with CTO-PCIs outside Japan were excluded from this study because it may be difficult to continue the clinical follow-up and missing data would increase. Therefore, of these 4,205 CTO-PCIs, 2,846 CTO-PCIs performed in Japan were initially included in this study. However, the registry secretariat and independent core laboratory excluded 250 procedures due to missing data or inappropriate angiographic assessment of target lesions. Thus, 2,596 CTO-PCIs were investigated for this study. Figure 2 shows the steps taken for each procedure. For 724 cases (27.8%), PRA was chosen as the primary CTO-PCI strategy. In addition, approximately one-quarter of the cases in the PAA group were switched to a retrograde approach after the antegrade approach failed.
The baseline patient characteristics, baseline angiographic characteristics, and clinical results of this study are presented in Tables 1 and 2. There was a high prevalence of coronary risk factors such as hypertension (78.5%), dyslipidemia (77.5%), and diabetes mellitus (44.9%). The prevalence of male sex, dyslipidemia, multivessel disease, reattempted cases, and complex CTO lesion morphology (lesion length ≥20 mm, lesion tortuosity, lesion calcification, and morphology of the proximal cap) was significantly higher in the PRA group than in the PAA group. The J-CTO scores of the PRA group were significantly higher than those of the PAA group (PAA vs. PRA 1.9 ± 1.1 vs. 2.4 ± 1.1; p < 0.001).
The overall success rate of the procedures in this analysis was about 90% (guidewire success 92.0%; technical success 89.9%; and procedural success 88.8%). The clinical outcomes for PAA were significantly better than those for PRA (PAA vs. PRA for technical success 91.0% vs. 87.3%; p = 0.006). The total stent length and implanted stent size were significantly longer and bigger in PRA than those in PAA. Procedure times and contrast volume were significantly higher for PRA than for PAA. The reason of technical failure was mostly failed guidewire crossing in both groups. The incidence of in-hospital MACCEs and complications, such as coronary perforation and contrast-induced nephropathy, were <2%. The incidence of irradiation skin injury was 0.2%.
In the PAA group, 1,390 CTO-PCIs (74.2%) were performed using only the antegrade approach, with guidewire success 97.1% and technical success 95.5%. Parallel wire crossing was attempted in 14.4% of these 1,390 cases (technical success 82.5%), and IVUS-guided wire crossing was attempted in 3.2% of cases after antegrade guidewire escalation failed (technical success 75.0%), as shown in Figure 3. In the PRA group, 16.0% of cases (n = 116) were switched to the antegrade approach after the retrograde approach failed, and the technical success rate of those cases was 80.2%. Parallel wire crossing was attempted in 28.4% of these 116 cases (technical success 78.8%), and IVUS-guided wire crossing was attempted in 15.5% of these cases (technical success 88.9%).
Table 3 shows the difference in the baseline characteristics between the cases involving only the antegrade approach and the RRA cases. The prevalence of reattempted cases and the complex CTO lesion morphology was significantly higher in the RRA group, and the J-CTO scores of the RRA were also significantly higher (RRA vs. only the antegrade technique 2.2 ± 1.1 vs. 1.7 ± 1.1; p < 0.001).
The J-CTO scores, the prevalence of reattempted cases, the distribution of target vessels, and the collateral filling differed significantly between PRA and RRA (shown in Online Table 1). The distribution of ultimately used collateral channels in both PRA and RRA is shown in Figure 4. The septal channel was mostly used for the collateral channel crossing in both groups. There was no significant difference. The prevalence of cases that failed the collateral channel crossing in the RRA group showed a tendency to be higher than that for the PRA group. The technical success rate for PRA was significantly better than those for RRA (RRA vs. PRA technical success 78.0% vs. 87.3%; p < 0.0001, shown in Online Table 1).
Table 4 shows the differences between successful and failed cases in the overall, PAA, and PRA groups. In the failed cases, the J-CTO scores, severe lesion calcification, complex morphology of proximal cap (without a stump), prevalence of the side branch at the proximal cap, and long CTO lesions were significantly higher.
The distribution of the crossing strategies in the cases with guidewire success is shown in Figure 5. In cases using only antegrade approach, single wire crossing was mostly performed. Conversely, the prevalence of parallel wire crossing and IVUS-guided wire crossing was significantly increased in cases using antegrade approach after the retrograde approach failed. Reverse controlled antegrade and retrograde subintimal tracking was mostly performed in cases using the retrograde approach. In 76.8% of 405 cases with jeopardized collateral arteries, PCI for donor arteries was performed before CTO-PCI (PRA 80.6%; RRA 70.1%; p = 0.016).
Table 5 and Online Table 2 present the results of uni- and multivariate analyses investigating possible predictors of failed CTO-PCIs in the overall, PAA, and PRA groups. In all groups, severe lesion calcification was a strong predictor of procedure failure.
This is the first report to evaluate the clinical outcomes of primary CTO-PCI strategies adopted by highly experienced Japanese specialists following the ITT principle. The main findings of the present study were as follows: 1) Highly experienced Japanese specialists frequently chose the retrograde approach as the primary CTO-PCI strategy (in 27.8% of cases), especially for more complex CTO lesions, with a success rate of about 90%; 2) For intermediate CTO lesions (J-CTO score <2), these specialists mainly performed CTO-PCIs using the antegrade approach alone, with a very high success rate (more than 95%); 3) However, for RRA, the success rate decreased to <80%; 4) The specialists performed the parallel guidewire crossing and IVUS-guided wire crossing after the guidewire escalation failed during antegrade CTO-PCIs, with high technical success (75.0% to 88.9%); and 5) Severe lesion calcification was a strong predictor of failed CTO-PCIs.
Recently, reports from American and European CTO-PCI registries have been published (7,23). The overall technical success of CTO-PCI in the American registry was 90.0%, and the technical success rate for retrograde CTO-PCI in the European registry was 75.3%. The technical success rate in the present study was higher than those in the previous reports. In particular, the success rate for the antegrade approach was more than 90% using guidewire escalation, parallel wire crossing, and IVUS-guided wire crossing, without antegrade dissection/re-entry devices.
The retrograde approach was frequently used as the primary CTO-PCI strategy (our registry 27.8%; U.S. registry 19.0%; European registry 12.5%). Pre-procedural planning for CTO-PCI is very important, and identifying clinical and angiographic characteristics associated with procedural failure could lead to improved patient selection and overall success of CTO-PCIs. A prediction rule based on J-CTO scores has recently been applied to grading the difficulty of CTO-PCIs (19). A hybrid algorithm for CTO-PCIs has demonstrated that the primary retrograde approach is favored in cases with complex CTO morphology based on angiographic factors similar to those used in the J-CTO score (11,24). In the present study, the prevalence of reattempted cases and complex CTO lesion morphology was significantly higher in the PRA group than in the PAA group. This finding suggests that the assessment of target CTO morphology and pre-operative planning by Japanese specialists was similar to the assessment of the J-CTO score and the hybrid algorithm, and Japanese specialists frequently chose the retrograde approach as the primary CTO-PCI strategy for more complex CTO lesions. The retrograde approach could be a feasible procedure when the antegrade approach seems to be particularly difficult. However, this technique requires high skill and extensive experience with CTO-PCIs. The retrograde approach should be familiar to the highly experienced specialists selected for this registry, which may partly explain the high prevalence of the retrograde approach as the primary CTO-PCI strategy in this study.
In the present study, the technical success rate for PRA was 87.3%. In the PRA group, 16.0% of cases were switched to the antegrade approach after the retrograde approach failed, and the technical success rate of those cases was 80.2%. Parallel wire crossing was performed in 28.4% of cases and IVUS-guided wire crossing in 15.5% of cases. The technical success of each technique was high (parallel wire crossing 78.8%; IVUS-guided wire crossing 88.9%). A recent analysis showed that the success rate of antegrade guidewire crossing after retrograde failure was 74.8% to 54.6% and that IVUS-guided wire crossing contributed to the success of using the antegrade approach after the retrograde approach failed (25). In the present study, the technical success rate for parallel wire crossing and IVUS-guided wire crossing in the antegrade approach after failed retrograde approach was higher than in that previous study, which may partly explain the high success rate of PRA in this study.
The success rate for RRA was significantly lower than that for PRA even though the baseline characteristics of the RRA cases exhibited less complex CTO morphology than the PRA cases. There may have been no suitable collateral for the collateral channel crossing. In addition, the first antegrade failure may have led to deteriorated visualization of the CTO distal vessel because of antegrade dissection, higher surgeon/patient fatigue, and increased contrast consumption or radiation exposure, and these factors may have compromised the success of RRA.
In our study, the prevalence of patients with prior coronary artery bypass grafting (CABG) history (7.9%) was lower than those in U.S. (33.9%) and European (17.6%) registries (7,23). The technical success rate of CTO-PCI of a native coronary artery for cases with prior CABG was significantly decreased compared with that for cases without prior CABG, as described in the previous report (26). Similarly, in this study, the technical success rate for cases with prior CABG (overall 82.5%; PAA 83.3%; PRA 80.9%) was lower than that for cases without prior CABG (overall 90.6%; PAA 91.6%; PRA 87.9%; overall p < 0.0001; PAA p = 0.001; PRA p = 0.099). Univariate analysis showed prior CABG history was a negative predictor of CTO-PCI success; however, multivariate analysis did not show the same. These findings suggest that an important factor of CTO-PCI for cases with prior CABG history seems to be the existence of suitable collateral for the retrograde approach. For cases without suitable collateral arteries, parallel wire crossing and IVUS-guided wire crossing could contribute to the procedure success as described in the previous report (26). Simultaneously, the dissection re-entry technique is expected to provide better results for such cases.
Recently, some specialists have recommended the use of antegrade subintimal dissection/re-entry strategies as a second- or third-line strategy after the failure of conventional antegrade or retrograde techniques because of the availability of dedicated dissection/re-entry devices (such as the CrossBoss catheter and Stingray balloon and wires [Boston Scientific, Natick, Massachusetts]), which can make the procedure faster and safer (6,10,23,27). Although the success rate of antegrade subintimal dissection/re-entry strategies has been gradually improving (67% to 97.6%), these still carry the risk of perforation, which may not become evident until after stent implantation and periprocedural myocardial infarction because of the occlusion of coronary side branches and collateral circulation. Previous reports have shown a high incidence of procedural complications (myocardial infarction 2.4% to 16%; coronary perforation 2.4% to 14.3%) (27). In the present study, the incidence of MACCEs and other complications was low. One explanation for this low complication rate may be that all of the CTO-PCI procedures were performed without an antegrade subintimal dissection/re-entry strategy.
Multivariate analysis showed that severe lesion calcification was a strong predictor of the failure of CTO-PCIs. The J-CTO score was developed to estimate technical success in CTO-PCI, and lesion calcification was one of the independent predictors for failed procedures (19). We have previously reported that lesion calcification was an independent predictor of failure of the retrograde approach even after successful collateral channel crossing, as in antegrade CTO-PCIs (20). Severe calcification remains an important problem even in CTO-PCI performed by skilled specialists.
A major disadvantage was the lack of standardized PCI procedures, such as for patient selection and guidewire selection, which depended on the decisions of each specialist. Thus, it lacks approaches that would have more clinical implication for less experienced specialists. Second, all CTO-PCIs were performed by highly skilled, experienced specialists and so the results may not be generalized to the daily clinical practice of less experienced specialists. Third, this study is based on the results of the procedures of the individual operators, not a randomized/multicenter trial. All operators are certified CTO-PCI operators; however, there is a possibility that the difference between the experience and skill among the operators influenced the results.
This study evaluated the clinical outcomes of primary CTO-PCI approaches taken by highly experienced Japanese CTO-PCI specialists, analyzing these according to the ITT principle. The overall technical success rate was high, and the complication rate was low. In this study, the retrograde approach was frequently chosen as the primary CTO-PCI strategy, especially for more complex CTO lesions. For intermediate CTO lesions, CTO-PCI was mainly performed using only the antegrade technique. Severe lesion calcification remains an important issue in CTO-PCIs.
WHAT IS KNOWN? PCI for patients with CTOs, when performed by experienced operators, can enhance the success of the former.
WHAT IS NEW? This is the first study to evaluate the clinical outcomes of primary CTO-PCI approaches considered by highly experienced Japanese CTO-PCI specialists and to analyze them according to the ITT principle.
WHAT IS NEXT? Complex CTO lesion morphology is still an important issue for CTO-PCI procedural success, and further improvement of technologies for medical devices, such as guidewires and catheters, is required to improve the success rate.
The authors appreciate the great effort for this registry of the late Dr. Kazuaki Mitsudo and dedicate this paper to him. They also appreciate Drs. Harumi Katoh (Department of Cardiology, Clinical Research Center, Kurashiki Central Hospital, Ohara HealthCare Foundation, Okayama, Japan) and Yoshiharu Yamamoto (Clinical Research Center, Kurashiki Central Hospital, Ohara HealthCare Foundation, Okayama, Japan) for managing and analyzing all data for this study. The authors would like to thank Drs. Yasumi Igarashi, Hisayuki Okada, Tsutomu Fujita, Ryohei Yoshikawa, Satoru Otsuji, Yoshihiro Takeda, Kenya Nasu, Takenori Shibata, Yoshihisa Kinoshita, Yuichi Noguchi, Masahiko Ochiai, Satoru Sumitsuji, Shinya Okamoto, Kazuhiro Ahida, Kaname Takizawa, Akitsugu Oida, Yoshihito Yamamoto, Makoto Sekiguchi, Jiro Andoh, Wataru Nagamatsu, Masahisa Yamane, Yoshiki Uehara, Eisho Kyo, Takeshi Serikawa, Fumitake Hosaka, Kenji Kawajiri, Kinzo Ueda, Toru Takahahi, and Shigeru Nakamura for their patients’ enrollment in the present study.
Dr. Tsuchikane is a consultant for Asahi Intecc, Boston Scientific, and NIPRO Corporation. Dr. Katoh is a consultant for Asahi Intecc and NIPRO Corp.; and is board chairman of and stock holder in RetroVascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary artery bypass grafting
- chronic total occlusion
- intravascular ultrasound
- major adverse cardiac and cerebrovascular event(s)
- primary antegrade approach
- percutaneous coronary intervention
- primary retrograde approach
- rescue retrograde approach
- Received December 23, 2016.
- Revision received June 11, 2017.
- Accepted June 15, 2017.
- 2017 American College of Cardiology Foundation
- Tsuchikane E.,
- Katoh O.,
- Kimura M.,
- Nasu K.,
- Kinoshita Y.,
- Suzuki T.
- Galassi A.R.,
- Sianos G.,
- Werner G.S.,
- et al.
- Kimura M.,
- Katoh O.,
- Tsuchikane E.,
- et al.
- Rathore S.,
- Katoh O.,
- Matsuo H.,
- et al.
- Whitlow P.L.,
- Burke M.N.,
- Lombardi W.L.,
- et al.
- Brilakis E.S.,
- Grantham J.A.,
- Rinfret S.,
- et al.
- Hollis S.,
- Campbell F.
- Nuesch E.,
- Trelle S.,
- Reichenbach S.,
- et al.
- Sumitsuji S.,
- Inoue K.,
- Ochiai M.,
- Tsuchikane E.,
- Ikeno F.
- Werner G.S.,
- Ferrari M.,
- Heinke S.,
- et al.
- Morino Y.,
- Abe M.,
- Morimoto T.,
- et al.
- Karmpaliotis D.,
- Karatasakis A.,
- Alaswad K.,
- et al.
- Christopoulos G.,
- Kandzari D.E.,
- Yeh R.W.,
- et al.
- Teramoto T.,
- Tsuchikane E.,
- Matsuo H.,
- et al.
- Michael T.T.,
- Papayannis A.C.,
- Banerjee S.,
- Brilakis E.S.