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Primary vs Secondary Retrograde Approach in Chronic Total Occlusion Percutaneous Coronary Interventions
Abstract
Background. The retrograde approach to coronary chronic total occlusions (CTOs) can be used as the initial crossing strategy (primary retrograde) or after failure of antegrade crossing attempts (secondary retrograde). Methods. We compared baseline clinical and angiographic characteristics and procedural outcomes of primary vs secondary retrograde crossing for CTO percutaneous coronary intervention (PCI) among 2789 procedures performed at 34 centers between 2012 and 2021. Results. Retrograde CTO-PCI was performed as the primary crossing strategy in 1086 cases (38.9%) and as a secondary approach in 1703 cases (61.1%). Patients in the primary group had slightly lower left ventricular ejection fraction (49.1% vs 50.4%; P=.02), were more likely to have had prior coronary artery bypass graft surgery (52.9% vs 38.4%; P<.001), and had higher J-CTO (3.31 ± 0.98 vs 2.99 ± 1.09; P<.001) and PROGRESS-CTO (1.47 ± 0.92 vs 1.29 ± 0.99; P<.001) scores. Technical (81.4% vs 77.3%; P=.01) and procedural success rates (78.6% vs 74.1%; P<.01) were higher in the primary retrograde group, with no difference between in-hospital major adverse event rates (4.3% vs 4.0%; P=.66). Contrast volume (250 mL [interquartile range (IQR), 176-347] vs 270 mL [IQR, 190-367]; P<.001) and procedure time (175 minutes [IQR, 127-233] vs 180 minutes [IQR, 142-236]; P<.001) were lower in the primary group. Conclusions. Use of the retrograde approach as the primary crossing strategy is associated with higher rates of technical and procedural success and similar rates of in-hospital major adverse cardiac events compared with secondary retrograde CTO-PCI.
J INVASIVE CARDIOL 2022;34(9):E672-E677. Epub 2022 August 12.
Key words: percutaneous coronary intervention, chronic total occlusion, retrograde approach
The retrograde approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) significantly increases success rates, especially for complex lesions,1,2 but has been associated with higher complications rates.3,4 The retrograde approach can be used as the initial crossing strategy (usually in cases with proximal cap ambiguity, flush ostial occlusions, lesions with diffusely diseased distal vessel, or bifurcation at the distal cap) or after failure of antegrade crossing attempts.5 The frequency and outcomes of primary vs secondary retrograde crossing during CTO-PCI have received limited study and were the focus of the present study.
Methods
We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 2789 CTO-PCIs performed between 2012 and 2021 enrolled at 34 centers. Data collection was recorded in a dedicated online database (PROGRESS-CTO: Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; ClinicalTrials.gov identifier: NCT02061436). Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Minneapolis Heart Institute Foundation.6,7 REDCap is a secure, web-based application designed to support data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources. The study was approved by the institutional review board of each site.
Coronary CTOs were defined as coronary lesions with TIMI (Thrombolysis in Myocardial Infarction) grade 0 flow of at least 3 months in duration. Estimation of the duration of occlusion was clinical, based on the first onset of angina, prior history of myocardial infarction (MI) in the target-vessel territory, or comparison with a prior angiogram. Calcification was assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (involving >50% of the reference lesion diameter). Moderate proximal vessel tortuosity was defined as the presence of at least 2 bends >70° or 1 bend >90° and severe tortuosity as 2 bends >90° or 1 bend >120° in the CTO vessel. A procedure was defined as retrograde if an attempt was made to cross the lesion through a collateral vessel or bypass graft supplying the target vessel distal to the lesion. The primary retrograde group included cases in which the retrograde approach was the first crossing strategy, whereas the secondary retrograde group included cases in which the retrograde approach was used after failure of antegrade crossing attempts. Antegrade dissection/re-entry was defined as antegrade PCI during which a guidewire was intentionally introduced into the extraplaque space proximal to the lesion, or re-entry into the distal true lumen was attempted after intentional or inadvertent extraplaque guidewire crossing.
Technical success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as the achievement of technical success without any in-hospital major adverse cardiac event (MACE). In-hospital MACE included any of the following adverse events prior to hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft (CABG) surgery, tamponade requiring either pericardiocentesis or surgery, and stroke. MI was defined using the Third Universal Definition of Myocardial Infarction (type 4a MI).8 The Japanese CTO (J-CTO) score was calculated as described by Morino et al9 and the PROGRESS-CTO score as described by Christopoulos et al.10
Statistical analysis. Categorical variables were expressed as percentages and were compared using Pearson’s Chi-square test or Fisher’s exact test. Continuous variables were presented as mean ± standard deviation or median (interquartile range [IQR]) unless otherwise specified and were compared using the Student’s t test or Wilcoxon rank-sum test, as appropriate. The assumption of normality was evaluated using summary statistics and graphical displays (histograms and QQ-plots). All statistical analyses were performed using JMP, version 14.0 (SAS Institute). A P-value of <.05 was considered statistically significant.
Results
The retrograde approach was used as the primary crossing strategy in 1086 cases (38.9%) and secondarily after failure of antegrade crossing in 1703 cases (61.1%). The baseline clinical characteristics of the study patients are summarized in Table 1. Patients in the primary retrograde group had slightly lower left ventricular ejection fraction (49.1% vs 50.4%; P=.02) and higher rates of prior CABG surgery (52.9% vs 38.4%; P<.001). There was no other difference in baseline clinical characteristics between the 2 groups.
The baseline angiographic characteristics of the study lesions are illustrated in Table 2. The most common CTO target vessel was the right coronary artery (71%), although the left anterior descending artery was less frequently the target lesion in the primary retrograde group (12% vs 20%; P<.001). Lesions in the primary retrograde group were longer (40 mm [IQR, 25-60] vs 30 mm [IQR, 20-45]; P<.001) and more likely to have unfavorable characteristics, such as proximal cap ambiguity (67.4% vs 50.4%; P<.001) and blunt or stumpless proximal cap (69.2% vs 59.8%; P<.001). The J-CTO (3.31 ± 0.98 vs 2.99 ± 1.09; P<.001) and PROGRESS-CTO scores (1.47 ± 0.92 vs 1.29 ± 0.99; P<.001) were higher in the primary retrograde group.
Procedural techniques are summarized in Table 3. The type and frequency of the collateral channel used for the retrograde crossing are shown in Figure 1. Septal collaterals were commonly used in both groups (61.9% vs 63.4%), but saphenous vein grafts were used more often for retrograde crossing in the primary retrograde group (16% vs 10%; P<.001). Interventions in the secondary retrograde group required longer procedural time (180 minutes [IQR, 142-236] vs 175 minutes [IQR, 127-233]; P<.01) and fluoroscopy time (78 minutes [IQR, 59-101] vs 75 minutes [IQR, 55-100]; P=.05), higher air kerma radiation dose (1.8 Gy [IQR, 0.9-3.1] vs 1.4 Gy [IQR, 0.82.4]; P<.001), and greater contrast volume (270 mL [IQR, 190-367] vs 250 mL [IQR, 176-347]; P<.001) (Table 4).
The overall technical (81.4% vs 77.3%; P=.01) and procedural success rates (78.6% vs 74.1%; P<.01) were significantly higher in the primary retrograde group (Table 4 and Figure 2). The incidence of in-hospital MACE was 4.1% overall (115 patients) and was comparable in both groups (4.3% vs 4%; P=.66) (Table 4 and Figure 2. Procedural complications are summarized in Figure 3. The incidence of acute MI was significantly higher in the primary retrograde group (2.1% vs 1.1%; P=.03) as compared with the secondary retrograde group; however, pericardiocentesis (0.7% vs 1.8%; P=.02) was less frequent. Overall in-hospital mortality was low (0.9%) and similar in both groups (1.3% vs 0.7%; P=.08). There were no significant differences in the incidence of repeat PCI (0.37% vs 0.59%; P=.43), stroke (0.4% vs 0.2%; P=.52), or perforation (8.8% vs 10.7%; P=.11).
Discussion
To the best of our knowledge, our study is the largest to date comparing a primary vs secondary retrograde approach for CTO-PCI. The major findings are the following: (1) primary retrograde CTO-PCI was associated with higher rates of technical and procedural success compared with secondary retrograde; (2) the overall in-hospital major adverse events were similar in both groups, although acute MI was more common and pericardiocentesis less common in the primary retrograde group.
The retrograde crossing strategy differs from the standard antegrade approach in that the lesion is approached from the distal vessel with a guidewire advanced through either a bypass graft or through collateral channels (septal or epicardial).11 The retrograde approach can be used as the initial crossing strategy (primary retrograde) in some cases, usually in long and tortuous CTOs with ambiguous proximal cap, diffusely diseased distal vessel or a bifurcation at the distal cap.12 The retrograde strategy can also be used as a secondary option (secondary retrograde) after failure of antegrade crossing attempts.11,12
In our study, higher success rates were observed when the retrograde approach was the primary strategy, compared with its use after antegrade crossing failure (81.4% vs 77.3%; P=.01). These results are similar to a study by Galassi et al,13 who analyzed 1582 CTO interventions performed using the retrograde approach as primary (76.2%) or secondary (23.8%) crossing strategy. In this study, the primary retrograde strategy was more successful than the secondary retrograde approach (82.2% vs 53.1%; P<.001). Karmpaliotis et al14 reported that retrograde CTO-PCI was performed in 462 of 1374 patients either as the primary technique (46%) or after failed initial antegrade crossing (54%). The technical success rate for primary retrograde was 83.4% vs 79.7% for retrograde attempts after antegrade crossing failure (P=.32). El Sabbagh et al15 performed a meta-analysis of 3482 retrograde CTO-PCI patients from 26 studies. A primary retrograde approach was used in 52.4%, procedural success was 83.3%, and the rates of emergency CABG, MI, and tamponade were 0.7%, 3.1%, and 1.4%, respectively, suggesting that the retrograde approach may carry increased risk of complications.
There are multiple potential explanations for the higher success rate of a primary retrograde approach. First, primary antegrade crossing attempts are successful in many cases, with failing cases likely having more adverse angiographic characteristics. Second, antegrade crossing may cause a complication requiring retrograde bailout. Third, primary retrograde cases may be more efficient, especially in very complex lesions, in which antegrade crossing is less likely to be successful.16
Our results do not necessarily imply that retrograde should be the first crossing attempt in a certain group of lesions. Although some lesions may be more suited to the retrograde approach (such as flush ostial CTOs), an initial antegrade approach is usually preferred for most lesions, as antegrade crossing overall carries less risk than the retrograde approach. Some of the complications of retrograde CTO-PCI may be life threatening (such as donor vessel injury, thrombosis, or multi-territory ischemia).
Our study demonstrates that use of the retrograde approach as the initial crossing strategy has similar rates of in-hospital MACE compared with secondary retrograde CTO-PCI. The incidence of urgent CABG, repeat PCI, stroke, or perforation was similar in the 2 groups and pericardiocentesis (0.7% vs 1.8%; P=.02) was less frequent in the primary retrograde group. However, the incidence of acute MI was significantly higher in the primary retrograde group.
Study limitations. PROGRESS-CTO is an observational retrospective study without long-term follow-up and no core laboratory assessment of the study angiograms or clinical event adjudication. The procedures were performed at dedicated, high-volume CTO centers by skilled and experienced operators, and these results may not be reproducible by less experienced operators. The decision regarding use of the retrograde approach as the primary or secondary CTO crossing strategy was at the discretion of the operator, and therefore our study is subject to selection bias.
Conclusion
The use of retrograde approach in CTO-PCI as the primary crossing strategy is associated with higher rates of technical and procedural success and similar rates of in-hospital MACE compared with secondary retrograde CTO-PCI.
Acknowledgments. The authors are grateful for the philanthropic support of our generous anonymous donors, and the philanthropic support of Drs Mary Ann and Donald A Sens, Mrs Diane and Dr Cline Hickok, Mrs Wilma and Mr Dale Johnson, Mrs Charlotte and Mr Jerry Golinvaux Family Fund, the Roehl Family Foundation, and 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.
Affiliations and Disclosures
From 1Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota; 2Henry Ford Cardiovascular Division, Detroit, Michigan; 3Gagnon Cardiovascular Institute, Morristown Medical Center, New Jersey; 4Massachusetts General Hospital, Boston, Massachusetts; 5Emory University Hospital Midtown, Atlanta, Georgia; 6Cleveland Clinic, Cleveland, Ohio; 7University Hospitals, Case Western Reserve University, Cleveland, Ohio; 8Red Cross Hospital of Athens, Athens, Greece; 9The Christ Hospital, Cincinnati, Ohio; 10Wellstar Health System, Marietta, Georgia; 11UCSD Medical Center, La Jolla, California; 12Acibadem Kocaeli Hospital, Izmit, Turkey; 13Aswan Heart Center, Magdi Yacoub Foundation, Cairo, Egypt; 14Memorial Bahcelievler Hospital, Istanbul, Turkey; and 15North Oaks Health System, Hammond, Louisiana.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Alaswad: consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr Karmpaliotis: honoria from Boston Scientific, Abbott Vascular; equity in Saranas, Soundbite, Traverse Vascular. Dr Jaffer: sponsored research from Canon, Siemens, Shockwave, Teleflex, Mercator, Boston Scientific; consultant for Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, Intravascular Imaging; equity interest in Intravascular Imaging, Inc, DurVena; licensing arrangements to Massachusetts General Hospital with Terumo, Canon, Spectrawave, including the right to receive royalties. Dr Nicholson: consulting/proctoring for Abbott Vascular, Boston Scientific, and Medtronic; advisory board for Abbott Vascular, Boston Scientific, and Medtronic. Dr Rinfret: speaker and proctorship honoraria from Boston Scientific, Abbott Vascular Canada, Medtronic Canada, and Terumo US. Dr Khatri: personal honoria for proctoring and speaking from Abbott Vascular, Asahi Intecc, Terumo, Boston Scientific. Dr Poommipanit: consultant for Asahi Intecc, Abbott Vascular. Dr Riley: consultant and speaker for Boston Scientific, Medtronic, Asahi Intecc, and Shockwave Medical. Dr Patel: speakers’ bureau for AstraZeneca. Dr ElGuindy: consulting honoraria from Medtronic, Boston Scientific, Asahi Intecc, Abbott; proctorship fees from Medtronic, Boston Scientific, Asahi Intecc, Terumo; educational grants from Medtronic. Dr Abi-Rafeh: proctor and speaker honoraria from Boston Scientific, Abbott Vascular. Dr Garcia: Institutional research grants from Edwards Lifesciences, Medtronic, Abbott Vascular, Biotronik, and Boston Scientific; consultant for Neochord, Abbott Vascular, Medtronic, and Boston Scientific; proctor for Edwards Lifesciences. Dr Burke: consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr Brilakis: consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Elsevier, GE Healthcare, IMDS, InfraRedx, Medicure, Medtronic, Opsens, Siemens, and Teleflex; research support from Boston Scientific, GE Healthcare; owner, Hippocrates LLC; shareholder in MHI Ventures, Cleerly Health, Stallion Medical. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript accepted March 17, 2022.
Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Director of the Center for Complex Coronary Interventions, Minneapolis Heart Institute, 920 E. 28th Street #300, Minneapolis, MN 55407. Email: esbrilakis@gmail.com
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