Chronic total occlusions (CTOs) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes after CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 patients with previous CABG who underwent CTO-PCI in 12 international centers in 2019 to 2023 were categorized into “grafted” and “ungrafted” groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into “graft-occluded” and “graft-patent” groups, depending on graft patency. The primary end points were (1) technical success rate, (2) target vessel failure, and (3) CTO failure rates at 1 year. CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs 80%, p = 0.004) than nongrafted CTOs. Of the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs 81%, p = 0.022). An occluded graft was an independent predictor of technical failure (odds ratio 2.04, 95% confidence interval 1.03 to 4.76, p = 0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1 year (hazard ratio 5.6, 95% confidence interval 1.2 to 27.5, log-rank p = 0.033). In conclusion, in patients with previous CABG who underwent CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure.
Highlights
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Enhanced complexity in grafted vessel lesions impacts procedural success.
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Patent grafts correlate with improved immediate procedural outcomes.
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Graft patency after chronic total occlusions (CTO)-percutaneous coronary intervention predicts CTO failure at follow-up.
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Intentional closure of patent grafts may be beneficial after CTO-percutaneous coronary intervention .
The presence of coronary chronic total occlusion (CTO) is an advanced and end-stage manifestation of atherosclerosis. The convergence of reduced blood flow and shear stress, accompanied by inadequate downstream perfusion in the myocardial region, may accelerate the plaque remodeling process. This triggers a self-perpetuating cycle, leading to negative remodeling and accelerated atherosclerosis, particularly evident in native vessels of patients who underwent coronary artery bypass grafting (CABG) surgery. As a consequence, CTO lesions in CABG patients show extensive calcification compared with CTOs in those without CABG. , The hypothesized mechanism involves hemodynamic changes, including blood stasis and reduced shear stress because of competitive flow between the native and bypass graft. Patients with a history of CABG and venous grafts exhibit a graft failure rate as high as 50% to 60% within 10 years. , In instances of graft failure, performing percutaneous coronary intervention (PCI) of the native vessel, as opposed to treating the graft, has been shown to have superior efficacy. Therefore, when facing a diseased yet patent graft, performing a CTO-PCI of the native vessel emerges as the most pragmatic approach. However, the technical implications associated with an occluded versus patent graft and, more importantly, the hemodynamic consequences of a patent graft maintaining persistent competitive flow after successful CTO-PCI of the native vessel continue to be debated and have not been systematically studied. Therefore, this study aimed to evaluate (1) the procedural implications of having a patent graft for CTO-PCI and (2) the impact of competitive flow from a patent graft on the patency of the native vessel after a successful CTO-PCI.
Methods
This is a multicenter, investigator-initiated study intended to collect data on patients with previous CABG who underwent CTO-PCI at 12 centers in 4 countries (Belgium, Canada, Italy, and the United Kingdom). Belgian centers prospectively collected data on consecutive CTO-PCIs for the Belgian Working Group on Chronic Total Occlusions registry, whereas the other centers collected data retrospectively. Each institutional ethics review board approved the study and all patients provided written informed consent to anonymously collect data. The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.
All patients with previous CABG who underwent CTO-PCI between 2019 and 2023 were enrolled in the study. The exclusion criteria were (1) patients treated with CABG <1 year before the CTO-PCI procedure to allow adequate time for the development of native coronary artery disease and exclude those who underwent a hybrid revascularization strategy and (2) patients with missing data on selective angiography of the vascular grafts. Each center provided patient-level data using a predesigned case report form.
All patient demographic, clinical, procedural, and anatomic data were systematically obtained for all patients. Subsequently, our cohort was initially categorized into 2 groups based on the presence or absence of a graft on the native CTO vessel, the “grafted” and “ungrafted” groups, respectively. The grafted group was further stratified according to graft patency. Those with a completely occluded graft were assigned to the “graft-occluded” group. Those with (partially) patent grafts were assigned to the “graft-patent” group, as illustrated in Figure 1 . Of note, all instances of partially patent grafts showed a stenosis of 70% or greater.
All coronary angiograms (from diagnostic procedure to the follow-up angiogram) were reviewed by a centralized core laboratory (Hartcentrum ZNA Middelheim, Antwerp, Belgium, EP) to provide a meticulous assessment of graft disease and flow before and after CTO-PCI and of outcomes.
Additional methods information is available in the Supplementary Methods section. ,
Comparing the graft-occluded versus graft-patent groups, our primary end points were technical success rate and the target vessel failure (TVF) at 1-year follow-up, a composite end point of cardiovascular death, any myocardial infarction (MI), or target vessel revascularization at follow-up. Notably, any MI involving the CTO vessel could result from either in-stent restenosis and/or thrombosis of the native CTO vessel or embolization from the graft to the native vessel. However, because of the study limitations, it was not possible to distinguish between these 2 potential causes of MI.
Furthermore, to examine the impact of competitive flow and graft patency on the durability of the result after a successful native CTO-PCI, we conducted a comparative analysis of CTO failure rates at the 1-year follow-up. This analysis was restricted to patients who underwent a successful CTO-PCI in the grafted group, and CTO failure rates were determined in groups with a persistently patent or occluded graft after CTO-PCI. For this analysis, we compared the outcomes according to final patency of the graft after CTO-PCI. We specifically compared the outcomes for final graft Thrombolysis in Myocardial Infarction (TIMI) flow 3 versus TIMI flow <3 ( Figure 2 ). CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis, the latter defined as a binary in-stent restenosis of 50% or greater, for which a conservative management was chosen. Finally, an additional objective of our analysis was to provide a description of vascular graft flow evolution after CTO-PCI of the native vessel.
Categorical variables are presented as frequencies and percentages, and statistical analysis was conducted using the chi-square test or Fisher’s exact test. Continuous variables are reported as mean ± SD or median and twenty-fifth to seventy-fifth percentile and compared using the Wilcoxon rank sum test or the Mann–Whitney U test, when appropriate. Freedom from TVF and CTO failure at 1-year follow-up rates were reported using the Kaplan–Meier method, and comparisons were performed using the log-rank test. To determine the predictors of technical failure, logistic regression models were used to provide adjusted odd ratios (ORs) with 95% confidence intervals (CIs). First, a univariate logistic regression was performed for each clinical, angiographic, and procedural variable. Any variable with a p <0.10 was entered into the multivariable logistic regression model. In this way, the number of variables was limited to 1 per ≥10 events to prevent overfitting of the model. The variables in the final model included blunt proximal CTO cap, previous CTO-PCI failure, the Japanese CTO (J-CTO) score, and a total occlusion of the graft before the CTO-PCI procedure. Collinearity was assessed using variance inflation factor test and values <2.5 indicate absence of significant multicollinearity. Finally, to assess the impact of persistent competitive flow on the occurrence of TVF at 1 year, Cox proportional hazards regression models were used to provide adjusted hazard ratios with 95% CIs. The model was constructed using the variable selection process as previously described. The variables in the final multivariable model included diabetes status, chronic kidney disease, and patient gender as fixed-effect factors. All statistical analyses and graphics were performed using R software version 4.2.2 (Foundation for Statistical Computing, Vienna, Austria). Statistical significance was established at p <0.05 (2-tailed) for all tests.
Results
Between January 2019 and August 2023, 1,800 patients underwent CTO-PCI in the participating centers. Of these, 259 (14.3%) had previously undergone CABG >1 year before the index procedure. Within the overall population, 60 CTO vessels (23%) were ungrafted, whereas 199 CTO vessels (77%) were grafted. Specifically, in patients who underwent CTO-PCI in grafted vessels, 140 (70%) were in the graft-occluded group and 59 (30%) were in the graft-patent group ( Figure 1 ). Detailed comparisons between the ungrafted and grafted groups are listed in Supplementary Tables 1 to 4 .
Overall, the median age was 71 years (interquartile range 67 to 73 years). As listed in Table 1 , common cardiovascular risk factors were well-balanced across the groups.
| Characteristic | Graft-occluded group, N = 140 (70%) | Graft-patent group, N = 59 (30%) | P-value |
|---|---|---|---|
| Age | 71 (65, 76) | 73 (63, 77) | 0.8 |
| Female sex | 22 (16%) | 12 (21%) | 0.4 |
| BMI | 27.7 (24.7, 31.4) | 28.0 (25.8, 30.8) | 0.8 |
| Smoking status | >0.9 | ||
| Former | 68 (49%) | 29 (49%) | |
| Current | 17 (12%) | 8 (14%) | |
| Hypertension | 113 (81%) | 49 (83%) | 0.7 |
| Dyslipidemia | 122 (87%) | 53 (90%) | 0.6 |
| Diabetes | 58 (41%) | 26 (44%) | 0.7 |
| Prior myocardial infarction | 79 (56%) | 39 (66%) | 0.2 |
| Prior PCI | 92 (66%) | 40 (68%) | 0.8 |
| Peripheral artery disease | 36 (26%) | 22 (37%) | 0.11 |
| Prior stroke | 10 (7%) | 7 (12%) | 0.3 |
| Chronic kidney disease (eGFR <30mL/min) | 24 (17%) | 15 (25%) | 0.2 |
| LVEF | 0.5 | ||
| >60% | 47 (34%) | 15 (25%) | |
| 51-60% | 49 (35%) | 20 (34%) | |
| 41-50% | 24 (17%) | 15 (25%) | |
| 31-40% | 14 (10%) | 5 (9%) | |
| <30% | 5 (4%) | 4 (7%) | |
| Positive ischemia test | 100/108 (93%) | 34/39 (87%) | 0.3 |
Grafted CTO lesions exhibited significantly higher complexity than ungrafted CTOs, as evidenced by increased values on the J-CTO (1.90 ± 1.05 vs 2.83 ± 1.05, p <0.001) and Prospective Global Registry for the Study of Chornic Total Occlusion Intervention (PROGRESS-CTO) scores (1.65 ± 1.29 vs 2.35 ± 1.49, p <0.001) ( Supplementary Table 2 ). An in-depth examination of the grafted CTO lesions revealed no difference in terms of complexity characteristics between the graft-occluded and graft-patent groups. However, as anticipated, patients with a patent graft more frequently exhibited a clearer visualization of the distal landing zone (p <0.001). Notably, in the patent group, the main vessel providing collaterals for distal visualization was the bypass in 4 of 5 cases, whereas contralateral native vessels were the predominant collaterals in half of the cases for the graft-occluded group (p <0.001) ( Table 2 ).
| Characteristic | Graft-occluded group, N = 140 (70%) | Graft-patent group, N = 59 (30%) | p-value |
|---|---|---|---|
| CTO artery | 0.043 | ||
| Left main stem | 3 (2%) | 0 (0%) | |
| Left anterior descending | 13 (9%) | 14 (24%) | |
| Right coronary artery | 87 (62%) | 30 (51%) | |
| Left circumflex artery | 37 (27%) | 15 (25%) | |
| CTO segment | 0.8 | ||
| Ostial | 20 (14%) | 7 (12%) | |
| Proximal | 60 (43%) | 27 (46%) | |
| Mid | 46 (33%) | 22 (37%) | |
| Distal | 14 (10%) | 3 (5%) | |
| In-stent CTO | 14 (10%) | 5 (8%) | 0.7 |
| Proximal cap side branch | 63 (45%) | 23 (39%) | 0.4 |
| Distal cap side branch | 64 (47%) | 30 (51%) | 0.6 |
| CTO length > 20mm | 66 (47%) | 35 (59%) | 0.12 |
| Bend >45° | 85 (62%) | 39 (66%) | 0.6 |
| Calcification moderate-to-severe | 105 (75%) | 46 (78%) | 0.7 |
| Blunt stump | 82 (59%) | 30 (51%) | 0.3 |
| Reattempt | 38 (27%) | 8 (14%) | 0.038 |
| Collateral filling | <0.001 | ||
| Contralateral | 68 (49%) | 5 (8%) | |
| Ipsilateral | 45 (32%) | 7 (12%) | |
| Contra- and Ipsi-lateral | 21 (15%) | 0 (0%) | |
| Bypass | 6 (4%) | 47 (80%) | |
| Good distal visualization | 65 (46%) | 44 (75%) | <0.001 |
| J-CTO score | 2.80 ± 1.01 | 2.84 ± 1.07 | 0.8 |
| PROGRESS-CTO score | 2.24 ± 1.52 | 2.40 ± 1.48 | 0.5 |
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