Predictors of Successful Primary Antegrade Wiring in Chronic Total Occlusion Percutaneous Coronary Intervention

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Background. Antegrade wiring is the most commonly used chronic total occlusion (CTO) crossing technique.

Methods. Using data from the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436), we examined the clinical and angiographic characteristics and procedural outcomes of CTO percutaneous coronary interventions (PCIs) performed using a primary antegrade wiring strategy.

Results. Of the 13 563 CTO PCIs performed at 46 centers between 2012 and 2023, a primary antegrade wiring strategy was used in 11 332 (83.6%). Upon multivariable logistic regression analysis, proximal cap ambiguity (odds ratio [OR]: 0.52; 95% CI, 0.46-0.59), side branch at the proximal cap (OR: 0.85; 95% CI, 0.77-0.95), blunt/no stump (OR: 0.52; 95% CI: 0.47-0.59), longer lesion length (OR [per 10 mm increase]: 0.79; 95% CI, 0.76-0.81), moderate to severe calcification (OR: 0.73; 95% CI, 0.66-0.81), moderate to severe proximal tortuosity (OR: 0.67; 95% CI, 0.59-0.75), bifurcation at the distal cap (OR: 0.66; 95% CI, 0.59-0.73), left anterior descending artery CTO (OR [vs right coronary artery]: 1.44; 95% CI, 1.28-1.62) and left circumflex CTO (OR [vs right coronary artery]: 1.22; 95% CI, 1.07-1.40), non-in-stent restenosis lesion (OR: 0.56; 95% CI, 0.49-0.65), and good distal landing zone (OR: 1.18; 95% CI, 1.06-1.32) were independently associated with primary antegrade wiring crossing success.

Conclusions. The use of antegrade wiring as the initial strategy was high (83.6%) in our registry. We identified several parameters associated with primary antegrade wiring success.

Antegrade wiring is the most commonly used and the most often successful crossing strategy for coronary chronic total occlusions (CTOs), especially for simpler occlusions.^1-4 Advanced CTO crossing techniques, such as antegrade dissection and re-entry (ADR) or the retrograde approach, are often required for complex CTOs.⁵ We examined parameters associated with successful CTO crossing using antegrade wiring technique as the initial strategy in CTO percutaneous coronary intervention (PCI).

Patient population. Using data from the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436), we analyzed the baseline clinical and angiographic characteristics and procedural outcomes of primary antegrade CTO PCI cases that were performed at 46 US and non-US centers between 2012 and 2023. We compared the outcomes of technically successful vs unsuccessful procedures using a primary antegrade strategy. Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the Minneapolis Heart Institute Foundation.^6,7 The study was approved by the institutional review board of each center.

Definitions. Coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration were defined as coronary CTOs. The occlusion duration was estimated clinically, based on the first onset of angina, prior history of myocardial infarction (MI) in the target vessel territory, or comparison with a prior angiogram. Use of a primary antegrade strategy was defined as an attempt to cross the CTO with a guidewire in an intraplaque antegrade manner as the first strategy, with no entry into the extraplaque space. Successful primary antegrade strategy was defined as successfully crossing the lesion with the primary antegrade strategy. Unsuccessful primary antegrade cases were defined as unsuccessful primary antegrade crossing attempt(s), regardless of whether non-antegrade crossing strategies were subsequently attempted, and regardless of the final result.

Angiography was used to evaluate calcification, categorizing it as mild (spot-like), moderate (involving a reference lesion diameter of ≤ 50%), or severe (> 50%). Effective revascularization of CTO resulting in less than 30% residual diameter stenosis within the treated segment and the restoration of TIMI grade 3 antegrade flow was considered technical success. The achievement of technical success without any major adverse cardiac events (MACE) during the hospital stay was considered procedural success. In-hospital MACE encompassed events such as death, myocardial infarction (MI), recurrent symptoms necessitating urgent repeat revascularization of the target vessel through PCI or coronary artery bypass graft (CABG) surgery, tamponade requiring pericardiocentesis or surgery, and stroke. MI was defined according to the Third Universal Definition of Myocardial Infarction (type 4a MI).⁸ Evaluation for procedural MI was done at site level. All angiographic variables and clinical outcomes were site-determined.

The Japanese CTO (J-CTO) score was calculated based on the description by Morino et al,⁹ the PROGRESS-CTO score based on the description by Christopoulos et al,¹⁰ the new PROGRESS-CTO complication scores (acute MI, MACE, mortality, and pericardiocentesis) based on the description by Simsek et al,¹¹ and the PROGRESS-CTO perforation score based on the description by Kostantinis et al.¹²

Statistical analysis. Categorical variables were expressed as percentages and compared using the Pearson’s chi-square test. Continuous variables were presented as mean ± standard deviation or as median (interquartile range) unless otherwise specified and were compared using the independent-samples t-test for normally distributed variables and the Mann-Whitney U test for non-parametric variables, as appropriate. Confounder selection for multivariable logistics regression was based on reasonable assumptions of causal effects on successful lesion crossing using primary antegrade wiring. To account for between-center differences influencing outcomes, a mixed-effects multivariable model was used with a random intercept per study center. Collinearity was assessed using a variance inflation factor (VIF) test and values less than 5 indicated absence of significant multicollinearity (Supplemental Table). To assess trend significance, the Mann-Kendall trend test was used.

R Statistical Software, version 4.2.2 (R Foundation for Statistical Computing) was used to perform all statistical analyses. A P-value of less than .05 was considered statistically significant.

Patient characteristics. Among 13 563 CTO PCIs performed at 46 centers between 2012 and 2023, primary antegrade wiring was used in 11 332 (83.6%). The use of primary antegrade wiring in CTO PCI increased over time (P for trend = .011) (Figure 1). Patients in whom a primary antegrade wiring strategy was successful were less likely to be men. They also had a higher prevalence of diabetes and a lower prevalence of hypertension, heart failure, cerebrovascular disease, and peripheral arterial disease, prior history of PCI and MI, and prior CABG (Table 1). After adjusting for history of prior MI in the area perfused by the totally occluded vessel, a history of prior PCI was no longer associated with successful primary antegrade wiring.

Angiographic and procedural characteristics. The angiographic characteristics of the study lesions are shown in Table 2. Lesions located in the left anterior descending artery (LAD) were more likely to be successfully crossed using primary antegrade wiring (64.4% vs 54.4%; P < .001). Lesions that were not crossed using primary antegrade wiring exhibited greater angiographic complexity, with longer occlusion length, higher prevalence of proximal cap ambiguity, side branch at the proximal cap, blunt/no stump, moderate to severe calcification, and moderate to severe proximal tortuosity, and lower prevalence of in-stent occlusion. The presence of interventional collaterals and a good distal landing zone were more common in cases with successful primary antegrade wiring. Lesions that were not crossed using primary antegrade wiring had higher J-CTO and PROGRESS-CTO complexity scores, and higher PROGRESS-CTO complications scores. The primary antegrade wiring attempt and success rates by J-CTO score are presented in Figure 2.
 

Procedure (138.00 vs 85.00 mins; P < .001) and fluoroscopy (56.65 vs 29.00 mins; P < .001) times were longer in unsuccessful primary antegrade wiring cases, whereas air kerma radiation dose (2.80 vs 1.61 Gy; P < .001), contrast volume (240.00 vs 180.00 mL; P < .001), and number of stents (2.50 ± 1.08 vs 1.96 ± 0.95; P < .001) were higher, compared with successful primary antegrade wiring cases (Table 2).

Among the 4842 cases where primary antegrade wiring was unsuccessful, successful crossing was ultimately achieved when ADR and retrograde wiring were used as the second crossing strategy in 1673 (34.6%) and 1967 (40.6%) cases, respectively, and as the third crossing strategy in 416 (8.6%) and 478 (9.9%) cases, respectively.

Multivariable logistic regression model. Upon multivariable logistic regression analysis (Figure 3), proximal cap ambiguity (odds ratio [OR]: 0.52; 95% CI, 0.46-0.59), side branch at the proximal cap (OR: 0.85; 95% CI, 0.77-0.95), blunt/no stump (OR: 0.52; 95% CI, 0.47-0.59), longer lesion length (OR [per 10-mm increase]: 0.79; 95% CI, 0.76-0.81), moderate to severe calcification (OR: 0.73; 95% CI, 0.66-0.81), moderate to severe proximal tortuosity (OR: 0.67; 95% CI, 0.59-0.75), bifurcation at the distal cap (OR: 0.66; 95% CI, 0.59-0.73), left anterior descending artery CTOs (OR [vs right coronary artery]: 1.44; 95% CI, 1.28-1.62) and left circumflex CTOs (OR [vs right coronary artery]: 1.22; 95% CI, 1.07-1.40) , non-in-stent restenosis occlusions (OR: 0.56; 95% CI, 0.49-0.65), and good distal landing zone (OR: 1.18; 95% CI, 1.06-1.32) were associated with primary antegrade wiring success.

Procedural and in-hospital outcomes. The overall technical success in primary antegrade wiring cases was 87.5%. Successful lesion crossing with primary antegrade wiring was associated with a lower in-hospital MACE (0.9% vs 3.1%; P < .001), death (0.2% vs 0.6%; P = .001), acute MI (0.2% vs 0.7%; P = .006), emergency CABG (0.0% vs 0.2%; p = 0.038), and pericardiocentesis (0.5% vs 1.5%; P < .001) (Table 3) when compared with unsuccessful primary antegrade wiring. Perforation (1.6% vs 7.5%; P < .001) and dissection/thrombus (0.3% vs 0.8%; P < .001) were also significantly less common in successful primary antegrade wiring cases (Table 3).

The principal findings of our study are as follows: (a) primary antegrade wiring was used in 83.6% of CTO PCI cases, (b) patients in whom primary antegrade wiring was successful had a lower prevalence of comorbidities and less complex lesions, and (c) several parameters were associated with lesion crossing using primary antegrade wiring (proximal cap ambiguity, side branch at the proximal cap, blunt/no stump, longer lesion length, moderate to severe calcification, moderate to severe proximal tortuosity, bifurcation at the distal cap, left anterior descending artery and left circumflex CTOs, non-in-stent occlusion, and good distal landing zone).

Antegrade wiring remains the most commonly used crossing strategy in CTO PCI.¹ A primary antegrade wiring strategy was used in the majority (83.6%) of our cases, which is similar to the Europe-based RECHARGE (REgistry of Crossboss and Hybrid procedures in FrAnce, the NetheRlands, BelGium and UnitEd Kingdom) registry (77%)⁴ and the Asia-based Japanese CTO-PCI expert registry (74.2%),² but higher than the US-based OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry (54.7%).³ In our registry, the use of primary antegrade wiring has been increasing over time, with 61.2% of 2012 cases using primary antegrade wiring, compared with 88.1% of 2023 cases.

Numerous algorithms have been created to aid operators in choosing the initial CTO crossing approach. Antegrade wiring is the favored initial crossing technique in all of these algorithms. However, for some complex lesions, such as those with proximal cap ambiguity, poor distal vessel quality, long occlusion length, calcification, and tortuosity, a primary retrograde approach or primary ADR can be used.¹³ The results of our study are in agreement with the recommendations of the global CTO crossing algorithm, since proximal cap ambiguity, poor distal landing zone, bifurcation at the distal cap, longer lesion length, moderate/severe calcification, and moderate/severe tortuosity were associated with unsuccessful CTO crossing with primary antegrade wiring (Figure 3).

CTOs located in the left anterior descending (LAD) or the left circumflex (LCX) coronary arteries were more likely to be successfully crossed using primary antegrade wiring compared with lesions located in the right coronary artery (RCA). In a meta-analysis of 69 886 patients who underwent CTO PCI, the RCA as the CTO target vessel was associated with technical success (odds ratio [OR]: 0.81; 95% CI, 0.76-0.88). Furthermore, Kostantinis et al showed that RCA CTOs are more complex and more likely to require use of the retrograde approach and ADR.¹⁴ Those findings potentially explain the higher likelihood of successfully crossing LAD or LCX lesions in cases where primary antegrade wiring was employed.

Limitations. Initially, PROGRESS-CTO is an observational registry with inherent limitations. There was no independent adjudication of clinical events. Additionally, there was no core laboratory analysis conducted on the angiograms in the study. Long-term follow-up data was not accessible for every patient. The operators within the PROGRESS-CTO registry are proficient in CTO PCI, which could potentially restrict the external applicability of the study's conclusions.

A primary antegrade wiring approach was used in 83.6% of CTO PCI cases. Proximal cap ambiguity, side branch at the proximal cap, blunt/no stump, longer lesion length, moderate to severe calcification, moderate to severe proximal tortuosity, bifurcation at the distal cap, target CTO vessel, non-in-stent occlusion, and distal landing zone quality were associated with the success of primary antegrade wiring.

From the ¹Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA; ²Texas Health Presbyterian Hospital, Dallas, Texas, USA; ³University Hospitals, Case Western Reserve University, Cleveland, Ohio, USA; ⁴Cleveland Clinic, Cleveland, Ohio, USA; ⁵Medical Center of the Rockies, Loveland, Colorado, USA; ⁶National Heart Institute, Cairo, Egypt^{; 7}WellSpan York Hospital, York, Pennsylvania, USA^{; 8}Biruni University Medical School, Istanbul, Turkey^{; 9}Massachusetts General Hospital, Boston, Massachusetts, USA^{; 10}Oklahoma Heart Institute, Tulsa, Oklahoma, USA; ¹¹Tristar Centennial Medical Center, Nashville, Tennessee, USA; ¹²St. Boniface General Hospital, Winnipeg, Manitoba, Canada; ¹³Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA; ¹⁴Henry Ford Cardiovascular Division, Detroit, Michigan, USA; ¹⁵Meshalkin Novosibirsk Research Institute, Novosibirsk, Russia; ¹⁶Selcuk University, Konya, Turkey; ¹⁷North Oaks Health System, Hammond, Louisiana, USA; ¹⁸Aswan Heart Center, Magdi Yacoub Foundation, Cairo, Egypt; ¹⁹Memorial Bahcelievler Hospital, Istanbul, Turkey; ²⁰The Promed Hospital, Chennai, India.

Acknowledgments: The authors are grateful for the philanthropic support of our generous Anonymous donors (2), and the philanthropic support of Drs. Mary Ann and Donald A Sens; Mr. Raymond Ames and Ms. Barbara Thorndike; Frank J and Eleanor A. Maslowski Charitable Trust; Joseph F and Mary M Fleischhacker Family Foundation; Mrs. Diane and Dr. Cline Hickok; Mrs. Marilyn and Mr. William Ryerse; Mr. Greg and Mrs. Rhoda Olsen; Mrs. Wilma and Mr. Dale Johnson; Mrs. Charlotte and Mr. Jerry Golinvaux Family Fund; the Roehl Family Foundation; the Joseph Durda Foundation. The generous gifts of these donors to the Minneapolis Heart Institute Foundation’s Science Center for Coronary Artery Disease (CCAD) helped support this research project.

Disclosures: Dr Choi serves on the Medtronic advisory board. Dr Poommipanit is a consultant for Asahi Intecc and Abbott Vascular. Dr Khatri has received personal honoraria for proctoring and speaking from Abbott Vascular, Medtronic, Terumo, Shockwave, and Boston Scientific. Dr Davies receives speaking honoraria from Abiomed, Asahi Intecc, Boston Scientific, Medtronic, Shockwave, and Teleflex, and serves on advisory boards for Abiomed, Avinger, Boston Scientific, Medtronic, and Rampart. Dr Jaffer has done sponsored research for Canon, Siemens, Shockwave, Teleflex, Mercator, and Boston Scientific; has been a consultant for Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, and Intravascular Imaging Inc; has equity interest in Intravascular Imaging Inc., and DurVena; and holds the right to receive royalties through Massachusetts General Hospital licensing arrangements with Terumo, Canon, and Spectrawave. Dr Azzalini received consulting fees from Teleflex, Abiomed, GE Healthcare, Asahi Intecc, Philips, Abbott Vascular, Reflow Medical, and Cardiovascular Systems, Inc.; serves on the advisory board of GE Healthcare; and owns equity in Reflow Medical. Dr Kearney reports consulting fees or honoraria from Asahi Intecc, Abiomed, Boston Scientific, Philips, Medtronic, Teleflex, and Reflow Medical. Dr Alaswad has been a consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr Abi‐Rafeh receives proctor and speaker honoraria from Boston Scientific and Shockwave Medical. Dr ElGuindy receives consulting honoraria from Medtronic, Boston Scientific, Asahi Intecc, and Terumo, and proctorship fees from Medtronic, Boston Scientific, Asahi Intecc, and Terumo. Dr Brilakis receives consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medicure, Medtronic, Siemens, Teleflex, and Terumo; research support from Boston Scientific, GE Healthcare; is the owner of Hippocrates LLC; and is a shareholder in MHI Ventures, Cleerly Health, and Stallion Medical. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Arun Kalyanasundaram, MD, MPH, Division of Cardiology, Promed Hospital,1/10A, East Coast Road, Kottivakkam, Chennai 600041, India. Email: arunksundaram@gmail.com

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