- Academic Editors
Background: Owing to advances in procedural techniques and the training
of interventional staff in catheterization labs, recent work has demonstrated the
safety of percutaneous coronary intervention (PCI) as a treatment for patients
suffering from chronic total occlusion (CTO). However, there has been little
research focused on systematic comparisons of PCI outcomes in CTO patients that
did or did not exhibit a history of previous coronary artery bypass grafting
(CABG). Methods: Electronic databases were systematically searched for
all studies comparing CTO-PCI outcomes for patients with and without a history of
CABG, with event rates subsequently being compared via random-effects models with
forest plots and odds ratios with 95% confidence intervals (CI), owing to the
assumption of between-studies heterogeneity. Results: In total, 8
observational studies enrolling 13,509 CTO patients were identified, including
3389 and 10,120 patients with and without a history of prior CABG, respectively.
Patients were enrolled in these studies from 1999–2018. Pooled analyses
indicated that CABG history was not linked to a lower proportion of radial access
24 (95% CI 0.52–1.03, p = 0.08), and a prior CABG history was linked
to a greater contrast volume (95% CI 0.12–0.44, p
Advances in procedural techniques and instrumentation have contributed to substantial improvements in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) safety and efficacy rates . When successful, CTO-PCI procedures can offer an effective alternative treatment option for patients with a history of coronary artery bypass grafting (CABG) experiencing angina following bypass graft failure. However, prior pathological analyses have suggested that CTO lesions in CABG patients exhibit pronounced negative remodeling and calcification not evident in patients without such a history [2, 3]. Accordingly, some studies have suggested CABG to be a predictor of CTO-PCI procedural failure . Moreover, the technical and procedural success rates for CTO-PCI have been reported to be lower in CABG patients without any corresponding increase in rates of in-hospital major complications [5, 6, 7]. However, further advances in the devices and materials used for these procedures have been developed since the publication of these prior studies, and it thus remains to be established as to whether these are associated with further improvements in clinical outcomes for treated patients. While one meta-analysis has explored this topic , it only analyzed four observational studies and there have since been several further published cohort studies, highlighting the need for an updated survey of the literature. This meta-analysis was thus performed with the goal of assessing procedural characteristics and clinical outcomes associated with CTO-PCI treatment of patients with and without a history of CABG.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to direct this meta-analysis. The protocol of this meta-analysis had been registered on PROSPERO registration. The registration number is CRD42022373092.
The PubMed, Embase, and Cochrane Central databases were systematically and independently searched by two investigators (YCS and SYH) for all relevant studies comparing CTO-PCI procedural characteristics and clinical outcomes between patients that did and did not exhibit a history of CABG published as of August 15, 2021. Search terms included the following: (1) chronic total occlusion, CTO, and coronary occlusion; (2) percutaneous coronary intervention and PCI; (3) coronary artery bypass, coronary bypass, bypass surgery, and CABG. No age or language restrictions were placed on these studies. Relevant clinical trials were further identified by searching http://www.clinicaltrials.gov, as well as the proceedings of major international cardiology meetings (American College of Cardiology, European Society of Cardiology, American Heart Association, Transcatheter Cardiovascular Therapeutics, and The Society of Cardiovascular Angiography and Interventions). References of selected studies were additionally reviewed in an effort to identify relevant articles.
Studies exhibiting original CTO-PCI procedure-related for patients with or without a history of CABG that included cardiovascular event incidence as a primary outcome were included in this meta-analysis. No randomized data control trials (RCTs) relevant to this topic were identified. Case reports, case series, editorials, reviews, and abstracts without a corresponding full-text article were excluded from these analyses.
Article titles and abstracts using the defined search strategy were independently reviewed by two investigators (YCS and SYH), with those articles meeting the inclusion criteria undergoing full-text review. Discrepancies were resolved by discussion and consensus. Evaluated procedural characteristics for included studies included radial access, contrast dosage, radiation dose and fluoroscopy time, procedural time, number of stents implanted and total stent length, technical failure, and procedural failure. Clinical complications included in this study were in-hospital death, periprocedural death, stroke, and periprocedural major adverse cardiovascular and cerebrovascular events (MACCE). Results were subject to sensitivity analyses to ensure the findings were robust, and study quality was assessed with the Newcastle-Ottawa scale for cohort studies.
The procedural characteristics of the enrolled studies included radial access,
contrast dosage, radiation dose and fluoroscopy time, procedural duration, number
and length of implanted stents, technical and procedural failure rates. Technical
success was defined as successful CTO revascularization with achievement of
The RevMan software program (version 5.4.1, The Cochrane Collaboration, London,
United Kingdom) was used to conduct the present meta-analysis. Data were compared
using random-effects models for all endpoints, with continuous variables being
reported as pooled standardized mean difference (SMD) values and categorical
values being reported with Mantel–Haenszel Odds Ratios (OR). All data pooled
analysis results were reported with 95% confidence intervals (CI).
Heterogeneity among studies was examined with Cochran’s Q test and
The PRISMA flow diagram corresponding to the study selection process for this meta-analysis is shown in Fig. 1. An initial search identified 2838 potentially relevant abstracts, of which 9 were subject to full-text review and 8 were ultimately enrolled in this study. These studies incorporated 13,439 patients, including 3349 and 10,090 with and without a history of CABG, respectively [5, 7, 9, 10, 11, 12, 13, 14]. All 8 studies were observational in design and had been published from 2013–2020, with follow-up durations ranging from 100 days to 32 months [5, 7, 9, 10, 11, 12, 13, 14]. Of these studies, 4 only assessed in-hospital outcomes [5, 7, 10, 13]. Details regarding study and patient characteristics are compiled in Table 1 [5, 7, 9, 10, 11, 12, 13, 14].
|Study||Characteristics||Study total size (n)||Age (y)||Male sex (%)||Body mass index (kg/m
||Diabetes (%)||Dyslipidemia (%)||Hypertension (%)||Current smoker (%)||Previous myocardial infarction (%)||Previous PCI (%)|
|[Azzalini 2018] ||Prior CABG||401||69.2
|No prior CABG||1657||64.3
|[Budassi 2021] ||Prior CABG||217||68.5
|No prior CABG||1035||64.9
|[Dautov 2016] ||Prior CABG||175||70
|No prior CABG||295||64
|[Michael 2013] ||Prior CABG||508||67.7
|No prior CABG||855||63.3
|[Nikolakopoulos 2020] ||Prior CABG||502|
|No prior CABG||1082|
|[Tajti 2019] ||Prior CABG||1101||67.3
|No prior CABG||2317||63.2
|[Teramoto 2014] ||Prior CABG||153||68.2 (62.4–74.6)||82||42||35||59||18|
|No prior CABG||1139||66.0 (58.2–73.6)||82||37||37||61||25|
|[Toma 2016] ||Prior CABG||292||68
|No prior CABG||1710||65
Study selection flow chart.
The proportion of radial access used in CTO-PCI was reported in four studies of
7266 patients, with high heterogeneity being detected for this endpoint
Forest plots corresponding to procedural characteristics. (A) Radial access. (B) Contrast dosage. (C) Radiation dose. (D) Fluoroscopy time. (E) Procedural time. (F) Number of stents implanted. (G) Total stent length. (H) Technical Failure. (I) Procedural failure. Risk ratios and pooled odds ratios with 95% CIs are displayed.
Six studies including 10,631 patients reported on contrast dosages, with high
heterogeneity for this endpoint (I
Seven studies [5, 7, 9, 10, 11, 12, 14] including 12,268 patients assessed radiation dose and fluoroscopy
time for the CTO-PCI procedure, revealing that individuals with a history of
prior CABG exhibited both an increase in radiation dose (SMD = 0.33, 95% CI
Six studies [5, 7, 9, 10, 11, 13] of 10,266 patients reported on procedural duration, with high
heterogeneity being evident for this endpoint (I
Implanted stent numbers and length were respectively reported by three [9, 10, 13] and four [9, 10, 11, 13]
studies. Patients exhibiting a history of CABG were implanted with more stents on
average (SMD = 0.51, 95% CI 0.41–0.60, p
Six studies [5, 7, 9, 11, 12, 13] enrolling 10,598 and 11,745 patients respectively reported on
technical failure and procedural failure rates. Patients exhibiting a history of
CABG exhibited higher rates of both technical failure (OR = 1.64, 95% CI
Seven studies reported 67 instances of in-hospital mortality among 11,850
patients, with no heterogeneity among studies (I
Forest plots corresponding to clinical outcomes. (A) In-hospital death. (B) Periprocedural death. (C) Stroke. (D) Periprocedural MACCE. Risk ratios and pooled odds ratios with 95% CIs are displayed.
Six studies reported 101 instances of periprocedural mortality among 10,266
patients, with no evidence of heterogeneity (I
In total, 25 instances of stroke were reported among 8629 patients in five
studies [5, 9, 10, 11, 13], with no significant heterogeneity (I
Overall, seven studies [5, 7, 9, 10, 11, 12, 13] assessed MACCE incidence as a composite endpoint,
including the incidence of procedure-related stroke, myocardial infarction,
urgent target vessel revascularization, tamponade necessitating either
pericardiocentesis or surgery, and death. This endpoint was not subject to any
significant heterogeneity (I
Funnel plots were used to assess potential publication bias, and exhibited slight asymmetry consistent with the potential for reporting bias, as smaller studies exhibited larger treatment effects (Fig. 4). The reliability of the evidence for each study outcome was assessed, as summarized in Supplementary Tables 1,2.
Funnel plot corresponding to publication bias.
This is the largest meta-analysis conducted to date comparing CTO-PCI procedural characteristics and clinical outcomes for patients with a history of CABG, assessing pooled data from 13,509 patients in 8 observational studies. The accumulation of further data has afforded greater statistical power such that these risk estimates are more precise and reliable than those in prior studies [5, 7, 8, 9, 10, 11, 12, 13, 14].
Here, procedural characteristics and clinical outcomes associated with the CTO-PCI procedure were compared as a function of whether or not patients had previously undergone CABG, ultimately revealing that patients with such a history exhibited increases in contrast dosage, radiation dose, fluoroscopy time, and both the number and total length of stents used for the CTO-PCI procedure as compared to patients without such a history, whereas radial access was less frequently utilized for these patients. Moreover, a history of CABG was associated with elevated rates of MACCE, stroke, periprocedural mortality, and in-hospital mortality.
These findings suggest that the CTO-PCI procedure may be more challenging when performed in individuals that have previously undergone CABG, contributing to lower rates of success and poorer clinical outcomes as compared to those in patients without such a medical history. The higher radiation dose, operative duration, contrast dosage, and rates of procedural failure attest to the increased difficulty of PCI in CABG patients while also suggesting that the CTO lesions in these patients may exhibit greater complexity. This may in part be attributable to the fact that CABG is the favored revascularization approach employed in patients exhibiting complex anatomical characteristics. Moreover, a history of prior CABG is associated with negative vascular remodeling and more rapid atherosclerotic disease progression following this procedure, resulting in further increases in procedural complexity. In a prior meta-analysis, we found CABG patients undergoing CTO-PCI to exhibit more complex lesion characteristics including higher J-CTO scores, longer lesion length, greater levels of calcification, and more proximal cap ambiguity . These results are shown in Supplementary Fig. 1. The Poorer clinical outcomes in individuals with a history of CABG may be attributable to their being older, exhibiting more comorbidities, and more frequently experiencing procedure-related complications. Our prior meta-analysis found prior CABG to be related to higher rates of procedural complications such as contrast-induced nephropathy, major bleeding, and perforation. A large cohort study of 2058 patients from Canada, Europe, and the USA published by Azzalini et al.  found lower rates of procedural success rates and higher rates of in-hospital complications in individuals with a history of CABG, with increased rates of target vessel failure of a medial 1-year follow-up period.
This study is subject to certain limitations. For one, all included studies were observational studies and they are thus susceptible to unknown confounds. Secondly, little long-term follow-up data were available for patients in either group. Thirdly, the heterogeneity of at least some of the studies included and the different time periods of the study which may influence the results [5, 7, 9, 10, 11, 12, 13, 14]. Lastly, the CTO-PCI technique has improved rapidly in recent years owing to technological and operative advances, and as such study age may have a significant impact on the associated procedural characteristics and clinical outcomes.
In summary, this meta-analysis suggests that CTO-PCI procedures may be more challenging and associated with worse outcomes when performed in patients that have undergone prior CABG, with these patients also exhibiting poorer in-hospital MACCE incidence and mortality rates relative to patients without a history of CABG.
YCS, SYH, and JHL conceived the study and designed the protocol; YCS and SYH integrated the data and drafted the manuscript; YKL and ZCC were responsible for the study selection, data extraction, and assessment of study quality; YCS and JHL revised the manuscript critically. All authors read and approved the final manuscript.
This study was supported by National Natural Science Fund of China (Nos. 82200441, 81970291 and 82170344); and the Major State Basic Research Development Program of China (973 Program, No. 2015CB554404).
The authors declare no conflict of interest.
Publisher’s Note: IMR Press stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.