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Outcomes Following Antegrade-Only Versus Retrograde Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the CCTOP Registry
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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of the Journal of Invasive Cardiology or HMP Global, their employees, and affiliates.
J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00130. Epub August 19, 2024.
Abstract
Background. Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be performed using an antegrade-only (AO) approach or a retrograde approach (RA). Whether an RA carries a higher risk of complications needs further investigation.
Methods. The Canadian CTO PCI (CCTOP) was a multicenter, prospective, investigator-initiated cohort study conducted at 6 experienced centers across Canada between March 2014 and October 2019. Patients who underwent an RA were compared to AO patients. The primary endpoint was in-hospital major adverse cardiac events (MACE), defined as death, any post-PCI cardiac enzyme elevation, urgent revascularization, and tamponade. A multivariable analysis was performed to control for potential confounders.
Results. A total of 1033 patients were included in the study, and an RA was used in 48.4% of the cases. The RA was associated with higher lesions complexity (J-CTO score 2.7 ± 1.1 vs 2.3 ± 1.1, P < .001) and lower technical success (81.2% vs 91.5%, P < .001). The risk of in-hospital MACE was higher with the RA (10.2% vs 4.7%, P < .001), and all deaths occurred in the RA group (0.8% vs 0%, P = .038). In the multivariable model, the RA remained associated with an increased risk of MACE (OR, 2.25; 95% CI, 1.26 to 4.02).
Conclusion. Our experience confirms that the RA is associated with an independent increased risk of in-hospital MACE when compared with an AO approach.
Introduction
Chronic total occlusions (CTO) are prevalent, diagnosed in one-fifth of coronary artery disease (CAD) patients undergoing coronary angiography.1,2 Successful revascularization of CTOs has been linked to several potential benefits such as decrease in ischemic burden, improvement of left ventricular ejection fraction (LVEF), reduction of arhythmic events, and even increased survival; however, the main indication to perform percutaneous coronary intervention (PCI) remains improvement in quality of life and angina relief, which has been shown to result from successful CTO PCI.3-12 The retrograde approach (RA) has revolutionized the treatment of CTO with PCI, substantially increasing its success rate over the last 2 decades When performed by expert operators, CTO PCI is expected to be successful in more than 85% of patients.13-23
Unfortunately, even with refractory angina, CTOs remain largely undertreated, especially when a percutaneous approach is preferred.7 This may be at least partially explained by risk aversion from clinicians and operators, as CTO PCI is associated with a higher risk of periprocedural complications compared with non-CTO PCI, especially when the RA is used.15,16,22,24-26 Whether the RA, often required for successful procedures, independently increases the risk of in-hospital complications remains a subject of debate.
Methods
Study design
The Canadian CTO PCI (CCTOP) was a multicenter, prospective, investigator-initiated cohort study, which captured over 300 variables from patients undergoing CTO PCI at 6 experienced centers across Canada between March 2014 and October 2019. All consecutive patients undergoing CTO PCI were included in the registry. Patients undergoing an Impella-supported CTO PCI with or without treating other lesions were excluded from this registry. The participants consented for entering the registry and Institutional Review Boards approved the study at each center. The study was compliant with the Declaration of Helsinki and Good Clinical Practice.
Study population
All patients undergoing CTO PCI and entering the CCTOP registry were considered for the analysis. Exclusion criteria included impossibility to determine if an antegrade-only (AO) or a RA was used, and when 2 CTO PCIs were performed during the same procedure.
Endpoints and definitions
Patients were classified in 2 groups: AO and RA. Patients for which an RA was used at some point during the procedure were classified as retrograde, and all others were classified as AO. A retrograde component of the procedure was considered even if the wire could not cross the collateral or graft retrogradely to the distal cap. Technical success was defined as achievement of stenting with a final Thrombolysis In Myocardial Infarction (TIMI) 3 flow. Procedural success was defined as technical success without in-hospital major adverse cardiac events (MACE). MACE was defined as the composite of death, any cardiac enzyme elevation, urgent revascularization, or tamponade. Coronary perforations were classified according to the Ellis classification, which has been previously described.27
The primary endpoint was the presence of any in-hospital MACE. Secondary endpoints included components of the primary endpoint, stroke, contrast-induced nephropathy, and other in-hospital adverse events.
Statistical analysis
Baseline, procedural and CTO characteristics were compared between the 2 groups. Continuous variables were reported as mean ± SD or as median with interquartile ranges (IQR), as appropriate. Categorical variables were presented as proportions. Continuous variables were compared using a Student’s t-test or a Wilcoxon rank sum test, as appropriate. A Pearson’s chi-square or a Fisher exact test was used for categorical variables, as appropriate.
Primary and secondary endpoints were analyzed depending on whether they were in the AO or RA group. A multivariable logistic regression was conducted among the whole study population for the primary endpoint that adjusted for the following characteristics: age, sex, prior coronary artery bypass graft (CABG), left ventricular ejection fraction (LVEF), coronary calcifications, CTO length, type of proximal cap, and femoral access use. These variables were selected based on a priori knowledge, and clinically relevant variables were included in the model.28 The primary endpoint was also analyzed over time, which was divided into tertiles. A logistic regression was performed, stratified by the CTO-PCI approach. Finally, a logistic regression was performed in the RA group to assess whether a primary retrograde vs a retrograde approach used as a second strategy was associated with the primary endpoint.
All statistical analyses were done with Stata/BE 17.0 (StataCorp).
Results
Baseline, procedural, and CTO lesions characteristics
During the enrollment period, a total of 1198 patients entered the registry. Of these patients, 1033 fulfilled the inclusion and exclusion criteria for this study (Figure 1). Baseline characteristics are shown in Table 1. A similar proportion of cases were performed with an RA vs an AO, with 48.4% of the patients being RA. The median age of the study population was 67 years (IQR 59-74) and 83.2% were male. Anterior ischemia was more common in the AO group (36.2% vs 28%, P = .048) and inferior ischemia was more frequent in the RA group (65.3% vs 55.3%, P = .020). Other baseline characteristics were similar in both groups, including a history of prior CABG (29.8% vs 24.8%, P = .068).
Angiographic and procedural characteristics by groups are presented in Table 2. The most frequent access combination overall was dual access using 1 radial and 1 femoral artery (45.9%). However, dual access was used more frequently in the retrograde group, with 96.7% in the retrograde group compared to 85.4% of cases in the antegrade group (P < .001). Procedures were in general longer in the RA group (174 [120-219] minutes vs 111 [85-150] minutes, P < .001) and led to higher radiation dose (3617 [2184-5263] mGray vs 2314 [1349-3607] mGray, P < .001). Lesion characteristics were consistently different between the 2 groups. The RCA was more frequently the target in the retrograde group (64.1% vs 44.7%, P < .001). Lesions in the RA group were more often calcified, (82.8% vs 74.0%, P < .001), more frequently longer than 20 mm (79.9% vs 52.1%, P < .001), and a blunt proximal cap was more common (43.5% vs 29.4%). The J-CTO score was higher in the retrograde group (2.7 ± 1.1 vs 2.3 ± 1.1, P < .001) (Figure 2), and the time to cross the CTO segment was longer with retrograde procedures (60 [25.5-105] minutes vs 20 [10-50] minutes, P < .001). In the RA group, a RA was the primary strategy in 38% of the cases. The most common retrograde pathway used in the RA group was through septal collaterals (71.7%), followed by epicardial collaterals (17.3%), and grafts (11.0%).
In-hospital outcomes
In-hospital outcomes are shown in Table 3. Technical success was less often achieved in the retrograde group (81.2% vs 91.5%, P < .001), as was the procedural success (73.4% vs 87.7%, P < .001) (Figure 3), compared with the AO group. Patients in the RA group had more in-hospital adverse events (10.2% vs 4.7%, P < .001), which were mostly driven by an excess of cardiac enzymes elevation (7.1% vs 3.4%, P = .007) and higher mortality (0.8% vs 0%, P = .038). Cardiac enzymes elevation was also more frequently the sole adverse event in the RA group (6.3% vs 3.1%, P = .03). There were also more type 2 and type 3 coronary perforations in the retrograde group (1.5% vs 0.9% and 2.1% vs 0.5%, P = .031). The risks of stroke (0.4% vs 0.2%, P = .52), contrast-induced nephropathy (1.4% vs 0.6%, P = .16), and major bleeding (0.6% vs 0.6%, P = .87) were similar between both groups.
In the multivariable analysis model, an RA remained associated with an increased risk of in-hospital MACE (OR 2.25, 95% CI 1.26 to 4.02). Results of the multivariable model are shown in Figure 4. The in-hospital MACE rate appeared to decrease over time in the RA group and remained stable in the AO group, as shown in Figure 5. In the RA group, there was no association between a primary retrograde approach and the primary endpoint (OR 1.32; 95% CI, 0.70-2.49).
Discussion
We described the practice surrounding CTO PCI in 6 experienced centers in Canada. Patients who underwent retrograde CTO PCI had an overall more complex coronary anatomy than patients who underwent an AO procedure. The overall technical and procedural success was comparable to other registries and higher in the AO compared with the RA group. In this study population, and as observed in previous studies, the risk of in-hospital complications was higher in the RA group.
The use of the RA varies considerably between different registries. Indeed, an RA was used in 29.9% of the lesions in the ERCTO registry, 36.7% of the patients in the PROGRESS-CTO, 45.9% of the lesions in the APCTO Club registry, 46.5% of CTOs in the Japanese Board of CTO Interventional Specialists registry, and 51.3% of the patients in the OPEN-CTO registry.15,22,24,29,30 In this Canadian population, the RA was used in 48.4% of the lesions, among the highest use in world experience.
In the present study, the risk of in-hospital MACE was higher in the RA group (10.2% vs 4.7%, P < .001). After adjustment for potential confounders, the association between the RA and MACE remained significant, with an OR of 2.25 (95% CI, 1.26-4.02). This finding is consistent with what was observed in other North American registries. In the OPEN-CTO registry, the risk of in-hospital adverse events was 10.8% in the retrograde group and 3.3% in the antegrade-only group (P < .001).24 In the PROGRESS-CTO registry, the risk of complications was 5.05% in the retrograde group and 0.81% in the antegrade-only group (P < .001).29 In both registries, a retrograde component of the CTO PCI was an independent predictor of adverse in-hospital outcomes. As such, in the Progress Complication score, a retrograde approach is associated with a 2-point increase in the score.31
On the other hand, others have reported lower absolute risk of complications following CTO PCI.3,13,15,16,19,26,32 This discrepancy regarding the absolute risk of adverse events is likely due to differences in outcomes definition. Many of the previous studies, like the present one, did not use standardized definitions, which all started before the standardization proposed by the CTO ARC consortium.33 More specifically, our study included any cardiac enzymes elevation in the composite endpoint, which likely increased the rate of in-hospital MACE compared with a stricter definition of myocardial infarction, especially in the RA group.34 With the recently published CTO Academic Research Consortium (CTO-ARC), future research should be more easily compared.33
Interestingly, in our study, the in-hospital MACE rate decreased from 14% in the first period tertile to 4% in the last in the RA group (P = .004), a finding that was not observed in the AO group (5% vs 9%, P = .549). In the PROGRESS-CTO registry, a decrease in complication rate was observed over time, but no difference was mentioned between retrograde and antegrade procedures.35 However, the risk of complication was higher with conventional reverse-controlled antegrade and retrograde tracking (CART), a technique that was used less frequently in recent years.36 This was not captured in our study. One other possible explanation for this encouraging trend is operators’ experience with the retrograde approach, which, by definition, increased overtime. In the ERCTO registry, higher CTO-PCI volume by operators was an independent predictor of successful retrograde CTO PCI; this could also apply to procedural complications.37
Limitations
Our study has several limitations. First, the observational nature of our study makes it vulnerable to unmeasured confounding. Patients in the RA group usually have more comorbidities and have a more complex coronary anatomy. Second, the lack of core lab assessment of angiographic results might have resulted in some variability of the assessment of technical success between operators. Third, our study did not include consistent long-term follow-up, and whether the immediate risk is associated with a poorer long-term prognosis in the current era remains unknown. Finally, these results do not apply to a more complex and high-risk but indicated patient (CHIP) population, as supported-CTO PCI patients were excluded.
Conclusions
The antegrade approach should remain the preferred approach when feasible, as suggested by the different available algorithms, as it is associated with lower in-hospital complications. However, when the complexity of the anatomy makes the antegrade approach impracticable or unsuccessful, the retrograde strategy may be used to achieve success, as failure is recognized as an independent factor for longer term mortality. Other known risk factors for complications such as age, calcifications, sex, and dissection and re-entry techniques must be carefully considered in addition to the retrograde approach. Clinical judgement and shared decision-making are paramount to weigh the risks of in-hospital complications and the benefits of angina relief with potential improved survival when choosing a retrograde strategy.
Affiliations and Disclosures
Louis Verreault-Julien, MD, MPH1; Israth Jahan, BSc2; Nandini Dendukuri, PhD2; Luiz F. Ybarra, MD, MBA2; Samer Mansour, MD3; Alexis Matteau, MD3; Harindra C. Wijeysundera, MD, PhD4; Anthony Fung, MBBS5; Simon Robinson, MD6,7; Jean-Michel Paradis, MD8; Can Manh Nguyen, MD7; Stéphane Rinfret, MD, SM2,9
From the 1St. Francis – Emory Healthcare, Columbus, Georgia, USA; 2McGill University Health Centre, Montreal, Quebec, Canada; 3Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada; 4Schulich Heart Centre, Division of Cardiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 5Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada; 6Division of Cardiology, Royal Jubilee Hospital, University of British Columbia, Victoria, British Columbia, Canada; 7Victoria Heart Institute Foundation, Victoria, British Columbia, Canada; 8Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Québec, Canada; 9Georgia Heart Institute, Northeast Georgia Medical Center, Gainesville, Georgia, USA.
Dr Verreault-Julien and Ms Jahan served a co-first authors of the manuscript.
Disclosures: Dr. Verreault-Julien receives speaker honorarium from Asahi and Shockwave. Dr Mansour receives unrestricted grant and speaker honorarium from Abbott vascular. Dr. Rinfret is a consultant for Teleflex and has received honoraria from Medtronic for proctoring. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.
Funding: The CCTOP registry was initially supported by an unrestricted research grant from Abbott Vascular Canada.
Address for correspondence: Stéphane Rinfret, MD, SM, FRCPC, FSCAI, FACC, Georgia Heart Institute, 200 South Enota Drive Northeast, Suite 200, Gainsville, GA 30501, USA. Email: srinfret@me.com; X: @RinfretStephane, @lvjulien_md
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