Original Contribution

Clinical Outcomes of Percutaneous Coronary Intervention for Chronic Total Occlusion in Native Coronary Arteries vs Saphenous Vein Grafts

Ahmad Shoaib, MD1; Thomas W. Johnson, MD2; Adrian Banning, MD3; Peter Ludman, MD4; Muhammad Rashid, PhD1; Jessica Potts, PhD1; Chun Shing Kwok, MBBS, PhD, MSc, BSc, MRCP(UK)1; Evan Kontopantelis, PhD5; Ziyad A. Azam, MBChB6; Tim Kinnaird, MD7; Mamas A. Mamas, DPhil1,5

Ahmad Shoaib, MD1; Thomas W. Johnson, MD2; Adrian Banning, MD3; Peter Ludman, MD4; Muhammad Rashid, PhD1; Jessica Potts, PhD1; Chun Shing Kwok, MBBS, PhD, MSc, BSc, MRCP(UK)1; Evan Kontopantelis, PhD5; Ziyad A. Azam, MBChB6; Tim Kinnaird, MD7; Mamas A. Mamas, DPhil1,5

Abstract: Background. There are limited data comparing outcomes of patients with previous coronary artery bypass grafting (CABG) presenting with stable angina who undergo percutaneous coronary intervention (PCI) to either a saphenous vein grafts (SVG) or a chronic total occlusion (CTO) in the native coronary arteries. We compared clinical characteristics and outcomes of these two groups in a national cohort. Methods and Results. We formed a longitudinal cohort (2007-2014; n = 11,132) of patients who underwent SVG-PCI (group 1; n = 8619) or CTO-PCI in native arteries (group 2; n = 2513) in the British Cardiovascular Intervention Society (BCIS) database. Median age was 68 years in both groups, but patients in group 2 were less likely to be female, had a higher prevalence of diabetes mellitus, hypertension, hypercholesterolemia, and previous myocardial infarction, as well as worsened angina and breathlessness, but history of prior stroke, renal diseases, and the presence of left ventricular systolic dysfunction were similar to group 1. Following multivariable analysis, no significant difference in mortality was observed during index hospital admission (odds ratio [OR], 1.70; 95% confidence interval [CI], 0.63-4.58; P=.29), at 30 days (OR, 1.81; 95% CI, 0.99-3.3; P=.05), and 1 year (OR, 1.11; 95% CI, 0.85-1.44; P=.43), nor was a significant difference found in in-hospital MACE rates (OR, 1.36; 95% CI, 0.85-2.19; P=.19). However, CTO-PCI was associated with more procedural complications (OR, 2.88; 95% CI, 2.38-3.47; P<.01) and vessel perforation (OR, 4.82; 95% CI, 2.80-8.28; P<.01) as compared with the SVG-PCI group. Risk of target-vessel revascularization at 1 year was similar (SVG-PCI 5.6% vs CTO-PCI 6.9%; P=.08). Conclusion. In this national cohort, CTO-PCI was performed in higher-risk patients, and was associated with more procedural complications but similar short-term or long-term mortality and in-hospital MACE. 

J INVASIVE CARDIOL 2020;32(9):350-357. Epub 2020 August 10. 

Key words: chronic total occlusion, coronary artery bypass grafting, percutaneous coronary intervention, saphenous vein grafts

Although coronary artery bypass graft (CABG) surgery is a common modality of treatment for patients with multivessel coronary artery disease, the longer-term patency of saphenous vein grafts (SVGs) is suboptimal. A significant proportion of SVGs (10%-40%) occlude within the first year, with a subsequent annual attrition rate of up to 5%.1-8 Furthermore, bypass grafting itself enhances the progression of atherosclerosis, thrombosis, and calcification in the native coronary tree, with up to 43% of bypassed native coronary arteries developing chronic total occlusion (CTO) after 1 year of surgery.9,10-12 Due to advanced age, frailty, and multiple comorbidities, further bypass surgery is rarely performed, leaving percutaneous coronary intervention (PCI) as the treatment of choice. However, PCI to SVGs is less efficacious than to native vessels. SVG-PCI is associated with lower success rates, higher complication rates, and poorer long-term outcomes (mortality, myocardial infarction [MI], and target-vessel revascularization [TVR]) as compared with PCI undertaken in native coronary vessels.13,14 In recognition of the poor long-term outcomes of SVG-PCI, there is a growing interest in treating native coronary artery disease when possible in such patients, even if the target lesions are CTOs. To date, there are no comparative data studying outcomes of SVG-PCI compared CTO-PCI in this patient cohort. Furthermore, there are only limited long-term outcomes data following CTO-PCI in patients with prior CABG. In an analysis of 2058 patients who underwent CTO-PCI, patients with prior CABG had greater procedural complexity, worse success rates, and higher adjusted risk of target-vessel failure (TVF) compared with non-CABG patients at a follow-up of 2 years.15,16

Current PCI guidelines do not provide guidance regarding whether PCI should be undertaken in the SVG or whether it is preferable to attempt to intervene in native CTO in this complex cohort with prior history of CABG due to limited evidence.17,18 There are no randomized controlled trial data available in this arena to define best practices. We therefore sought to describe the early (inpatient and 30-day) and late (1-year) clinical outcomes of SVG-PCI compared with native-vessel CTO-PCI in patients with prior CABG in a large, contemporary, unselected national cohort from the database of the British Cardiovascular Intervention Society (BCIS). 


We analyzed national data for all patients with prior history of CABG and a CTO in 1 or more native coronary vessels that had undergone PCI to either SVG or CTO in native coronary arteries in England and Wales from January 2007 to December 2014. The BCIS records data prospectively on PCI practice across the United Kingdom, and this process is overseen by the National Institute of Cardiovascular Outcomes Research (NICOR). The quality of these data has previously been validated and published.19,20 Informed consent is obtained from each patient before undertaking PCI procedures and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in a priori approval by the institution’s human research committee.

In 2013, 97.6% of all PCIs performed in a National Health Service (NHS) hospital in England and Wales were recorded on this national database (www.bcis.org.uk/). The BCIS database consists of 113 clinical, demographical, procedural, and outcomes variables, with approximately 80,000 new records added each year.21-23 BCIS data are linked with Office of National Statistics (ONS) records for mortality tracking in all patients from England and Wales by using their unique NHS number. Patients from Scotland and Northern Ireland were excluded because of the absence of the ONS-linked mortality data. Institutional research and ethical board approval were not required for this study, as all data were anonymized and routinely collected as part of the national audit. We excluded patients if the CTO-PCI was performed in the setting of an acute coronary syndrome or if the information was missing for age, sex, and mortality data after discharge (Supplemental Figure S1; all supplemental materials are available at www.invasivecardiology.com). Data were collected on patients’ clinical and demographic characteristics, risk profiles, and comorbid diseases, as well as aspects of interventional practice and adjunctive pharmacological therapy. All-cause mortality data were collected during index admission and tracked up to 1 year after discharge. We also analyzed in-hospital major adverse cardiovascular events (MACE), defined as a composite of in-hospital mortality, in-hospital MI, and TVR, and procedural complications, including coronary perforation and major in-hospital bleeding. In-hospital major bleeding was defined as a composite of clinical tamponade after coronary perforation, intracerebral bleed, gastrointestinal bleed, blood or platelet transfusion, retroperitoneal hematoma, or an arterial access-site hemorrhage. We also analyzed a composite endpoint of “any procedural complication,” which is defined in the BCIS dataset as any complication including aortic dissection, coronary perforation, heart block requiring pacing, DC cardioversion, no-flow/slow-flow phenomenon, need for ventilation, and shock induced by the procedure. We also analyzed prevalence of TVR within 30 days, 1 year, and at or anytime during the follow-up period. TVR was defined as a second procedure in the same CTO artery or SVG. For this analysis, we excluded patients where TVR data were not available. Furthermore, we analyzed temporal and geographical changes in interventional practice for these patients from 2007-2014.

A CTO lesion was defined as complete occlusion with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 antegrade through the affected segment of >3-month duration as per prior manuscripts derived from the BCIS registry.19 We also analyzed data by the number of enabling strategies used in the index procedure. Enabling strategies to facilitate CTO-PCI were defined as one of the following: dual arterial access, rotational or laser atherectomy, intravascular ultrasound (IVUS), use of penetration catheters (recorded in the BCIS dataset as Finecross [Terumo], Corsair [Teleflex Medical], Tornus [Asahi Intecc]) or CrossBoss/Stingray balloon (Boston Scientific).19 

Statistical analysis. The study participants were divided into group 1 (SVG-PCI) and group 2 (CTO-PCI in native arteries). For descriptive statistical analysis of demographics, procedural details, and unadjusted outcomes, continuous variables were reported as medians and interquartile ranges (IQRs), whereas categorical variables were reported using frequencies and proportions. Chi-square tests were applied to assess group differences for categorical variables, while rank-sum tests were used for continuous variables. We used multiple imputations with chained equations to impute data for all variables with missing information. We applied multivariable logistic regression analysis to estimate the risk of adverse outcomes between groups. 

Additionally, we performed propensity-score matching on imputed data to estimate the average treatment effect, adjusting for baseline differences between the two groups of interest. One-to-one matching with replacements was applied, followed by logistic regression analysis (the sole predictor being group membership) to gain the average treatment effect. We also performed Kaplan-Meier survival estimates for 30-day and 1-year mortality. Log-rank test was used to assess the difference between two groups. Stata version 14.2 statistical package was used for all analyses. All statistical analyses were two-tailed, and an alpha of 5% was used throughout.


Study cohort. Figure 1 summarizes our main study findings. Our study cohort consisted of 11,132 patients with prior history of CABG who had at least 1 CTO and who had PCI to either a SVG or CTO in the native coronary arteries in England and Wales from January 2007 to December 2014. The process of patient inclusion and exclusion is presented in Supplemental Figure S1. Out of 11,132 total patients, SVG-PCI was performed in 8619 (77%) and CTO-PCI in native arteries was performed in 2513 (23%) (Table 1). The median follow-up of the entire cohort was 4.61 years (IQR, 2.44-6.92 years). Moreover, we assessed temporal changes in practice for these patients from 2007-2014 (Supplemental Figure S2). There was a clear trend to adopt the CTO-PCI approach over time, as it was used in only 9% of cases in 2007 and steadily increased to 38% in 2014. We observed heterogeneous PCI practice in different areas, with clear preferences of one approach compared with the other (Supplemental Figure S3).

Clinical characteristics. Significant differences were observed in demographics, as well as in clinical and procedural characteristics, between the two groups (Table 1). Median age was 68 years in both groups. Compared with SVG-PCI patients, CTO-PCI patients were less likely to be female, had a higher prevalence of diabetes mellitus (DM), hypertension, hypercholesterolemia, previous MI, peripheral vascular disease, family history of coronary artery disease, and smoking history. In contrast, a history of previous stroke, renal diseases, and the presence of left ventricular systolic dysfunction were similar in both groups. Patients in group 1 were more likely to receive glycoprotein IIb/IIIa inhibitors (11% vs 6%; P<.001), drug-eluting stent (DES; 70% vs 60%; P<.001) and mechanical ventilatory support (1.33% vs 0.59%; P<.01). Utilization of enabling strategies was more frequent in CTO-PCI patients than in SVG-PCI patients (P<.001). 

Unadjusted clinical outcomes. The unadjusted (“crude”) mortality in group 2 was similar during index admission (0.14% vs 0.28%; P=.14), higher at 30 days (0.76% vs 0.38%; P=.02), but similar at 1 year (3.46% vs 3.10%; P=.36) compared with group 1 (Table 1). In-hospital transfusion of blood products (0.06% in group 1 vs 0.12% in group 2; P=.31), in-hospital stroke (0.06% in group 1 vs 0.00% in group 2; P=.23), and in-hospital MACE (0.75% in group 1 vs 1.09% in group 2; P=.10) were similar between the two groups. No stent was implanted in 8% of patients in group 1 and 35% patients in group 2 (Table 1). More patients in group 2 suffered from in-hospital major bleeding (1.29% vs 0.61%; P<.01), vessel perforation (1.60% vs 0.27%; P<.001), and any procedural complication (9% vs 3%; P<.01) compared with group 1. In unadjusted analysis, risk of TVR was similar at any time during the study period (8.46% vs 8.67%; P=.76), higher at 30 days (1.83% vs 0.70%; P<.001), and similar at 1 year (5.6% vs 7.27%; P=.08) in group 1 (SVG-PCI) vs group 2 (CTO-PCI) (Supplemental Figure S4; Table 1). 

Kaplan-Meier survival estimates at 30 days and 1 year are presented in Supplemental Figure S5. Subgroup analyses of clinical outcomes according to enabling strategies is presented in Supplemental Tables S1-S4. 

Adjusted clinical outcomes. The adjusted risks of procedural complications, short-term and long-term mortality, and in-hospital MACE are presented in Table 2. In the multivariable statistical analysis, the composite risk of any procedural complication was approximately 3 times higher (OR, 2.88; 95% CI, 2.38-3.47; P<.001) and vessel perforation was 5 times higher (OR, 4.82; 95% CI, 2.80-8.28; P<.001) in the CTO-PCI group vs the SVG-PCI group. After adjustment of baseline characteristics, no significant differences in mortality were observed between the groups during index admission (OR, 1.70; 95% CI, 0.63-4.58; P=.29), at 30 days (OR, 1.81; 95% CI, 0.99-3.31; P=.05), and at 1 year of follow-up (OR, 1.11; 95% CI, 0.85-1.44; P=.43). In addition, no significant differences in MACE were observed between the two cohorts (OR, 1.36; 95% CI, 0.85-2.19; P=.19) after adjustment of baseline covariates.

Analysis with propensity-score matching. In a propensity-score matching analysis, the adjusted composite risk of any procedural complication (OR, 2.99; 95% CI, 2.28-3.73; P<.001) and vessel perforation (OR, 4.75; 95% CI, 2.28-7.24; P<.01) were higher in the CTO-PCI in native arteries group vs the SVG-PCI group (Table 3). However, the adjusted risk of mortality during index admission (OR, 1.65; 95% CI, 0.75-4.07; P=.59), at 30 days (OR, 1.55; 95% CI, 0.34-2.78; P=.37), and at 1 year of follow-up (OR, 1.03; 95% CI, 0.62-1.45; P=.88) was similar between the two groups. 

Subgroup analyses. We performed sensitivity analyses in the patient subgroups with successful PCI and with only DES implantation. In multivariate analyses, we again observed higher risk of any procedural complication (OR, 2.68; 95% CI, 2.13-3.39; P<.001) and coronary artery perforation (OR, 4.55; 95% CI, 2.36-8.55; P<.001), but similar risk of short-term or long-term mortality and in-hospital MACE in the CTO-PCI group vs the SVG-PCI group (Supplemental Table S5). Similar results were obtained when we restricted our analyses to patients who received only DES implantation (Supplemental Table S6). 


In this large, contemporary, real-world study evaluating patients with prior history of CABG presenting with stable angina, undergoing PCI to either a SVG or to a CTO in a native coronary artery, we demonstrate a higher adjusted risk of any procedural complications and vessel perforation in CTO-PCI, but a similar adjusted risk of short-term and long-term mortality, TVR, and in-hospital MACE. We also show that PCI practice in this complex cohort of patients is heterogeneous, with some geographical areas more readily adopting a CTO-PCI approach in favor of SVG-PCI. Interestingly, we demonstrate a clear trend to undertake a greater proportion of CTO-PCI over time compared with SVG-PCI. To our knowledge, this is the only study, to date, that compares and contrasts clinical outcomes in prior CABG patients who have stable angina and at least 1 CTO that has undergone PCI to the SVG or a CTO in the native coronary arteries. 

Percutaneous intervention of the SVG can be challenging. Plaque burden, SVG angiographic severity score, female sex, the presence of thrombus, and old age are strongly associated with MACE.24-26 Angiographic lesion assessment in SVG intervention can be difficult and adjunctive assessment tools including IVUS, fractional flow reserve, optical coherence tomography, and instantaneous wave-free ratio are not well studied in randomized controlled trials in this group of patients. In an analysis of 11,118 patients (73% native artery and 27% SVG) with prior CABG who underwent PCI between 2005-2013 in 67 hospitals in the United States during a median follow-up of 3 years, SVG-PCI was associated with higher rates of mortality (adjusted hazard ratio [HR], 1.30; 95% CI, 1.18-1.42; P<.001), MI (adjusted HR, 1.61; 95% CI, 1.43-1.82; P<.001), and repeat revascularization (adjusted HR, 1.60; 95% CI, 1.50-1.7; P<.001) compared with PCI in native arteries.13 In a recently published randomized controlled trial comparing the risk and benefits of the use of DES vs bare-metal stent (BMS) in SVG-PCI, a high prevalence of adverse clinical outcomes was observed in both groups. At 12-month follow-up, the incidence of TVF was 17% (51/292) in the DES group vs 19% (58/305) in the BMS group (adjusted HR, 0.92; 95% CI, 0.63-1.34; P=.70). High proportions of other endpoints, like death from any cause (DES 8% vs BMS 7%), MI during follow-up (10% in both groups), TVR (DES 12% vs BMS 11%), and target-lesion revascularization (DES 9% vs BMS 8%), were observed in both cohorts, although these differences were statistically non-significant.27 

The poorer longer-term outcomes observed following SVG-PCI have driven many interventional cardiologists to target disease in the native coronary vessels, and in particular CTO lesions. With the emergence of modern algorithms, novel techniques, and advanced equipment, technical hurdles have become less challenging in CTO-PCI.28 Success rates range from 50%-70% if the antegrade approach is used as a sole strategy; with the addition of retrograde techniques and contemporary algorithms, the success rate can improve to >90%. However, technical success with CTO-PCI is challenging in patients with prior CABG due to lesion complexity, which curtails both antegrade and retrograde approaches.29 In a retrospective observational study of 1363 consecutive patients who underwent CTO-PCI in 3 tertiary-care hospitals in the United States, patients with prior CABG were older, had more comorbid conditions, were more frequently treated with retrograde technique (47% vs 27%; P<.001), and had lower proportion of procedural success (80% vs 88%; P=.02) vs those without previous history of CABG.30 In multivariable statistical analysis, history of previous CABG independently predicted lower technical success rate (OR, 0.49; 95% CI, 0.35-0.70; P<.001). Azzalini et al reported similar results in an analysis of 2058 patients (401 with prior CABG and 1657 with no prior CABG) who underwent CTO-PCI, patients with prior CABG had higher occlusion complexity RECHARGE (Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom) score (3.6 ±1.3 vs 1.8 ± 1.2; P<.001), lower procedural success rate (81% vs 87%; P<.001), and higher major complication rate (3.7% vs 1.5%; P<.01). At a median follow-up of 377 days (IQR, 277-766 days), TVF rate was higher in patients who previously received CABG than in non-CABG patients (16% vs 9%; P<.001). However, none of these major studies directly compared CTO-PCI with SVG-PCI in patients with previous history of CABG. 

This study provides important clinical insights into patients with prior CABG who have a CTO and the option to undertake either SVG-PCI or CTO-PCI. First, we report that CTO-PCI in the native arteries is associated with higher procedural complications (especially vessel perforation) as compared with SVG-PCI, which is likely due to the more complex techniques (dissection/re-entry, retrograde approach, and more aggressive use of enabling strategies) required in this patient subgroup. Second, vessel perforation can lead to tamponade, and CABG patients may still become compromised, because loculated effusions can develop and require surgical or computed tomography (CT)-guided drainage.31 The cause of perforation in these patients may be collateral channels damaged during the retrograde approach or aggressive balloon dilation in severely diseased vessels. Third, despite higher complication rates in the CTO-PCI group, in-hospital MACE and short-/long-term mortality rates were similar in the two groups. Interestingly, the crude incidence of TVR was similar at 1 year in the CTO and SVG cohorts. Our analysis suggests that the decision to undertake either CTO-PCI or SVG-PCI is not clear cut, with similar long-term mortality and TVR outcomes irrespective of the treatment strategy adopted. The decision to undertake PCI to either the native CTO or the SVG should depend on a number of factors, including the age of the graft and its level of degeneration, the complexity of the CTO lesion, and the experience of the operator with CTO techniques. 

Study limitations. First, this is a retrospective analysis of prospectively collected data with all the inherent bias ascribed to this kind of study design. Particularly, inferences may be confounded by unobserved differences in patients, differences in lesion characteristics across the two groups, and complexity of the lesions. Furthermore, the BCIS dataset does not provide insight into whether both treatment options were available to the operator, ie, whether there was a patent SVG supplying the same vascular territory as the CTO lesion, or whether there was a CTO in the same vascular territory as the SVG lesion that was intervened upon. Second, the BCIS registry does not capture information relating to CTO lesion complexity according to modern scoring systems32-36 or data regarding SVG characteristics, such as thrombus burden/degeneration. Third, the BCIS dataset does not capture information around SVG occlusion, which may be very relevant when deciding long-term strategies around revascularization. Fourth, although mortality tracking within England and Wales is well organized, all clinical outcomes and postprocedural complications are self-reported without formal adjudication. Hence, such clinical outcomes are vulnerable to reporting biases, and complications might be underreported, although it is unlikely that there will be differences in such reporting biases in the two studied groups. Finally, due to a lack of randomization, interventional strategy was at the discretion of the individual operator, and is therefore dependent on their clinical skills, surgical cover for complex procedures, and patients’ clinical characteristics and lesion complexity, which makes direct comparisons subject to a degree of confounding. 


Our analysis demonstrates a change in procedural strategy for intervention in patients with prior CABG, with a 4-fold increase in the adoption of native coronary CTO-PCI between 2007-2014. The CTO-PCI approach was associated with more procedural complications and vessel perforation compared with SVG-PCI, although in the multivariable analysis we did not observe any significant differences in in-hospital MACE or mortality outcomes in the short/long term once adjustments were made for differences in baseline characteristics. We report similar TVR rates in both groups. The decision to undertake PCI to either the SVG or CTO in this group of patients when both options are available should be determined by operator experience, age of the SVG, and complexity of the CTO, with similar outcomes reported in both patient groups in appropriately selected cases in the short/long term.

From the 1Keele Cardiovascular Research Group, Centre for Prognosis Research, Keele University, United Kingdom; 2Department of Cardiology, Bristol Heart Institute, Bristol, United Kingdom; 3Department of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom; 4Institute of Cardiovascular Sciences, Birmingham University, Birmingham, United Kingdom; 5Institute of Population Health, Manchester University, Manchester, United Kingdom; 6School of Medicine, University of Liverpool, Liverpool, United Kingdom; and 7Department of Cardiology, University Hospital of Wales, Cardiff, Wales.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Banning reports grant support to his institution from Boston Scientific; speaker fees from Boston Scientific, Abbott Vascular, and Medtronic. Dr Johnson reports personal fees from Abbott Vascular, Boston Scientific, Terumo, Vascular Perspectives, Medtronic, and Shockwave; grant support/non-financial support from Bayer and Astra-Zeneca. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted April 15, 2020.

Address for correspondence: Prof. Mamas A. Mamas, Keele Cardiovascular Research Group, Centre for Prognosis Research, Keele University, Stoke-on-Trent, United Kingdom. Email: mamasmamas1@yahoo.co.uk

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