Author + information
- Received September 21, 2015
- Revision received January 13, 2016
- Accepted January 28, 2016
- Published online May 9, 2016.
- Alfredo R. Galassi, MDa,∗ (, )
- Marouane Boukhris, MDa,b,
- Salvatore Azzarelli, MDa,
- Marine Castaing, MSca,
- Francesco Marzà, MDa and
- Salvatore D. Tomasello, MDa
- aDepartment of Clinical and Experimental Medicine, Catheterization Laboratory and Cardiovascular Interventional Unit, Cannizzaro Hospital, University of Catania, Catania, Italy
- bFaculty of Medicine of Tunis, University of Tunis El Manar, El Manar, Tunisia
- ↵∗Reprint requests and correspondence:
Prof. Alfredo R. Galassi, Department of Clinical and Experimental Medicine, Catheterization Laboratory and Cardiovascular Interventional Unit, Cannizzaro Hospital, University of Catania, 95021 Catania, Italy.
Objectives The aims of this study were to describe the 10-year experience of a single operator dedicated to chronic total occlusion (CTO) and to establish a model for predicting technical failure.
Background During the last decade, the interest in percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) has increased, allowing the improvement of success rate.
Methods One thousand nineteen patients with CTO underwent 1,073 CTO procedures performed by a single CTO-dedicated operator. The study population was subdivided into 2 groups by time period: period 1 (January 2005 to December 2009, n = 378) and period 2 (January 2010 to December 2014, n = 641). Observations were randomly assigned to a derivation set and a validation set (in a 2:1 ratio). A prediction score was established by assigning points for each independent predictor of technical failure in the derivation set according to the beta coefficient and summing all points accrued.
Results Lesions attempted in period 2 were more complex in comparison with those in period 1. Compared with period 1, both technical and clinical success rates significantly improved (from 87.8% to 94.4% [p = 0.001] and from 77.6% to 89.9% [p < 0.001], respectively). A prediction score for technical failure including age ≥75 years (1 point), ostial location (1 point), and collateral filling Rentrop grade <2 (2 points) was established, stratifying procedures into 4 difficulty groups: easy (0), intermediate (1), difficult (2), and very difficult (3 or 4), with decreasing technical success rates. In derivation and validation sets, areas under the curve were comparable (0.728 and 0.772, respectively).
Conclusions With growing expertise, the success rate has increased despite increasing complexity of attempted lesions. The established model predicted the probability of technical failure and thus might be applied to grading the difficulty of CTO procedures.
Percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) represent the most technically challenging procedures in contemporary interventional cardiology (1,2). During the past decade, important developments in equipment and techniques have led to the achievement of high rates of success and low rates of complications, as shown in registries from around the globe (3–5). Similar to the setting of acute coronary syndromes (6), the success and outcomes of CTO percutaneous attempts have been reported to be closely correlated with operators’ procedural volumes and expertise, particularly with the retrograde approach (7–9).
Recently, the J-CTO Registry (Japanese Multicenter CTO) led to the development of the J-CTO score to predict the likelihood of successful guidewire crossing within 30 min (10). Although this latter score has been shown to correlate with lesion complexity, its role in predicting CTO PCI success remains debatable (11,12).
In the present paper, we report the 10-year experience of a single CTO-dedicated operator, assessing the impact of J-CTO score on procedural details and success and trying to establish a prediction model for technical failure.
We conducted a retrospective analysis of consecutive patients with at least 1 native coronary artery CTO subjected to percutaneous recanalization attempts performed by a single expert interventional cardiologist (A.R.G.) from January 2005 to December 2014 inclusive.
All procedures were scheduled (not ad hoc PCI), and patients were selected on the basis of the presence of symptoms, viability of the myocardium subtended by the CTO artery, and inducible ischemia (>10%) in the CTO artery territory, as demonstrated by functional imaging tests. In patients with more than 1 CTO, only 1 CTO vessel was attempted per procedure. All CTO lesions were attempted only once. The sequence of use of wiring techniques and the guidewire selection were left entirely to the operator’s discretion.
According to the date of CTO PCI attempt, our study population was subdivided into 2 groups by time period: period 1 (January 2005 to December 2009) and period 2 (January 2010 to December 2014).
Informed consent was obtained from all patients, and the study was carried out in accordance with the principles of the Declaration of Helsinki.
Coronary CTOs were defined as angiographic evidence of total occlusions with TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 and estimated durations of at least 3 months (13).
Visible calcifications and vessel tortuosity were defined as previously described (10). Collateral filling of the CTO artery from other patent vessels was graded using the Rentrop classification: grade 0 = no visible filling of any collateral channel; grade 1 = filling of the side branches of the occluded artery, with no dye reaching the epicardial segment; grade 2 = partial filling of the epicardial vessel; and grade 3 = complete filling of epicardial vessel by collateral vessels. Technical success was defined as angiographic success (final residual stenosis <20% by visual estimation and TIMI flow grade 3 after CTO recanalization). Clinical success was defined as angiographic success with no in-hospital major adverse cardiac events (MACEs) or contrast-induced nephropathy (3,8). MACEs included cardiac death, Q-wave and non–Q-wave myocardial infarction (MI), tamponade, recurrent symptoms requiring urgent repeat target vessel revascularization (with either PCI or coronary artery bypass grafting). In all patients, creatine kinase–MB was evaluated 6 h after the procedure and until normalization if the levels were abnormal. Non–Q-wave MI was defined as creatine kinase–MB enzyme elevation >3 times the upper limit of normal (3,8). Contrast-induced nephropathy was defined as an increase of 25% or 0.5 mg/dl in serum creatinine level at 24 to 48 h after PCI in comparison with baseline values (3).
Assessment of lesion complexity
To classify the attempted CTO lesions according to their complexity, the J-CTO score was calculated as described by Morino et al. (10). Variability in J-CTO score reporting was assessed in a random sample of 10 CTO angiograms, which were evaluated by the same operator (for intraobserver variability) and another senior interventionalist (for interobserver variability). The lesions were classified as easy, intermediate, difficult, or very difficult if the J-CTO score was 0, 1, 2, or ≥3, respectively (10).
Descriptive statistics and comparisons
Clinical characteristics, angiographic features, and in-hospital events were reported through standard descriptive analyses for large samples assumed to follow a normal distribution. Continuous variables are presented as mean ± SD and categorical variables as frequencies and percentages. Student t tests and chi-square tests (or Fisher exact tests when at least 25% of values showed expected cell frequencies <5) were used for comparison between the 2 time-period groups and among J-CTO categories. A p value <0.05 was considered to indicate statistical significance.
We tried to identify clinical and/or angiographic factors predicting the success of the retrograde approach through stepwise logistic regression analysis. Univariate analysis was initially performed; univariate variables with p values < 0.10 were thereafter included in the multivariate model. Student t tests and chi-square tests (or Fisher exact tests when at least 25% of values showed expected cell frequencies <5) were used for comparison between antegrade and retrograde CTO procedures. A p value <0.05 was considered to indicate statistical significance.
J-CTO score association with procedural details and technical failure
The association of J-CTO score with procedural time, fluoroscopy time, and contrast load was assessed in linear regression; regression coefficients with their 95% confidence intervals (CIs) were calculated for a 1-point increase in J-CTO score. To evaluate the association between J-CTO score and technical failure, receiver-operating characteristic (ROC) curves and areas under the curve (AUCs) were used to assess discrimination, whereas the Hosmer-Lemeshow test was used to assess calibration.
Prediction model for technical failure
Observations were randomized in a 2:1 ratio in each period group and thereafter assigned to the derivation and validation sets, respectively. The univariate relationships between technical failure and categorical variables in the derivation set were evaluated using chi-square tests with appropriate degrees of freedom. Variables that showed significant differences (p < 0.05) were included in a forward multivariate logistic regression model that selected unsuccessful CTO PCI as the positive event. The meaningful independent predictors identified by multivariate analysis were used to develop a clinical prediction model. The difficulty score for a CTO procedure was determined by assigning points for each factor present (according to the beta coefficient) and then summing all points.
The resulting continuous distribution of total difficulty scores across all observations in the derivation set was then stratified into 4 categories of points that grouped procedures according to the level of difficulty (easy, intermediate, difficult, or very difficult). The chi-square test was used to compare the derivation and validation sets. The discriminatory performance of the model was validated by comparing the ROC curve analysis of the derivation set with that of the validation set.
All data were processed using SPSS version 21.0 (SPSS, Chicago, Illinois).
Baseline characteristics, procedural details, and outcomes
Our study population consisted of 1,019 patients (mean age 61.1 ± 9.7 years, 91.3% men) who underwent 1,073 CTO PCI attempts by a single CTO-dedicated operator from January 2005 to December 2014. The number of CTO procedures per year has increased to remain higher than 100 CTO PCIs per year since 2008 (except 2012), surpassing 150 CTO PCIs per year in 2009, 2010, and 2014. Despite increased difficulty of attempted CTO lesions, the technical success rate has improved, exceeding 90% since 2009 and reaching 95.4% in 2014. Similarly, the clinical success rate increased from 57.7% in 2005 to 92.1% in 2014 (Figure 1).
Periods 1 and 2 included 378 and 641 patients, corresponding to 411 and 662 CTO PCI procedures, respectively. Clinical and angiographic baseline characteristics are presented in Tables 1 and 2, respectively. In comparison with period 1, more period 2 patients were male and had diabetes. Smoking, renal dysfunction, prior revascularization, and multivessel coronary artery disease were less common in period 2 than in period 1. In period 2, patients were less often asymptomatic and showed better preserved left ventricular ejection fractions.
With regard to the angiographic characteristics, CTO lesions attempted in period 2 were more often visibly calcified and tortuous. Moreover, the period 2 lesions were longer and had been subjected more often to previous unsuccessful attempts. Thus, more lesions classified as very difficult (J-CTO score ≥3) were attempted in period 2 compared with period 1 (56.6% vs. 29.4%; p < 0.001).
Table 3 shows the procedural details and immediate outcome of CTO PCI attempts. In the majority of cases, drug-eluting stents were implanted, with greater stent length in period 2. Compared with period 1, both technical and clinical success rates significantly improved (from 87.8% to 94.4% [p = 0.001] and from 77.6% to 89.9% [p < 0.001], respectively), whereas no differences in procedural time, fluoroscopy time, and contrast load were observed. Significant decreases in in-hospital MACEs (2.6% vs. 5.8%; p < 0.001) and contrast-induced nephropathy (2.6% vs. 10.9%; p < 0.001) were achieved in period 2 in comparison with period 1.
A retrograde approach was performed in 292 CTO procedures (27.2%): as a first approach in 233 cases (79.8%) and after antegrade failure in 59 cases (20.2%). The evolution of retrograde use as the first strategy and its outcomes are shown in Online Figure 1. Since 2012, >30% of CTO lesions have been initially attempted with a retrograde approach.
The overall technical and clinical success rates of retrograde CTO attempts were 75% and 68.4%, respectively. The retrograde approach was more often successful when used as the first-line strategy than after a failed antegrade approach (78% vs. 55.9%; p < 0.001). Since 2010, the Sion guidewire (Asahi, Japan) and Corsair microcatheter (Asahi, Japan) have been used to negotiate retrograde collateral vessels in 96.8% and 91.9% of retrograde cases, respectively. Successful retrograde routes were septal collateral vessels in 77.6% of cases, epicardial collateral vessels in 19.3%, and bypass grafts in 3.1%. The successful retrograde techniques were as follows: retrograde wire crossing (34.2%), touching wire technique (22.8%), controlled antegrade retrograde tracking (14.7%), and reverse controlled antegrade retrograde tracking (28.3%). Multivariate analysis identified the following variables as independent predictors of retrograde approach success: age (10-year increase) (odds ratio [OR]: 0.76; 95% CI: 0.58 to 0.98; p = 0.038), disease of the distal segment of the CTO artery (OR: 0.49; 95% CI: 0.25 to 0.96; p = 0.037), the presence of CC2 collateral vessels (OR: 3.48; 95% CI: 1.83 to 6.62; p < 0.001), and retrograde approach use as first-line strategy (OR: 3.10; 95% CI: 1.53 to 6.30; p = 0.002).
Table 4 summarizes procedural details and immediate outcome of antegrade and retrograde procedures. In both periods, retrograde CTO attempts were more time- and contrast-consuming procedures compared with antegrade attempts (p < 0.01 for all). Retrograde attempts were associated with higher occurrence of tamponade (3.1% vs. 0.6%; p = 0.001) and in-hospital MACEs (5.8% vs. 2.8%; p < 0.001). Contrast-induced nephropathy was less frequently observed after CTO retrograde attempts performed during period 2 (14.8% vs. 2.8%; p < 0.001).
J-CTO score association with procedural details and technical failure
Calculation of J-CTO score was highly reproducible, with identical scores reported in 9 of 10 assessed CTO lesions (kappa values were 0.935 for both intra- and interobserver reproducibility).
In both periods, very difficult lesions were significantly associated with longer procedural time, longer fluoroscopy time, and greater use of contrast. Compared with period 1, in the presence of J-CTO score <3, significant reductions in procedural and fluoroscopy times and in contrast load were observed in period 2, whereas in lesions with J-CTO scores ≥3, no significant differences were found between the 2 periods (Figure 2).
Overall, for every 1-point increase in J-CTO score, procedural time increased by 17.47 min (95% CI: 14.19 to 20.75 min; p < 0.001), fluoroscopy time increased by 14.85 min (95% CI: 11.8 to 17.91 min; p < 0.001), and contrast load increased by 39.88 ml (95% CI: 28.65 to 51.11 ml; p < 0.001). Greater increases in these latter parameters were observed in period 2 in comparison with period 1 (Online Table 1).
With regard to the recanalization techniques, an increase in J-CTO score was associated with greater use of antegrade dissection re-entry techniques and a retrograde approach (Figure 3A). Compared with period 1, soft guidewires were substituted for hard guidewires in period 2 and were the most commonly used, even for very difficult CTO lesions (Figure 3B, Online Figure 2).
The Hosmer-Lemeshow test revealed a lack of fit between J-CTO score and technical failure (chi-square = 7.817; p = 0.05), and ROC curve analysis demonstrated low discrimination (AUC = 0.556) (Figure 4).
Prediction model for technical failure
No differences in clinical and angiographic characteristics were observed between the derivation and validation sets (Online Table 2).
The univariate correlates of technical failure in the derivation set included age ≥75 years, history of MI, prior PCI, left ventricular ejection fraction <50%, previous attempt, ostial location, blunt stump, collateral filling Rentrop grade <2, disease of the distal segment of the CTO artery, and period 2 (Online Table 3). In multivariate analysis, 3 variables (age ≥75 years, ostial location, and collateral filling Rentrop grade <2) were found to be independent predictors of technical failure (Table 5).
To develop the clinical prediction rule, we assigned each of the 3 identified factors an integer score proportional to the beta coefficient. Thus, we decided to give 1 point to age ≥75 years and ostial location (beta coefficients of 0.850 and 0.691, respectively) and 2 points to collateral filling Rentrop grade <2 (beta coefficient of 1.390). The established ORA (ostial location, Rentrop grade <2, age ≥75 years) score was used to categorize CTO procedures in the derivation set into 4 groups with varying likelihood of success: 1) easy (score = 0); 2) intermediate (score = 1); 3) difficult (score = 2); and 4) very difficult (score = 3 or 4) (Figure 5). The probability of technical success in each group of CTO procedures (easy, intermediate, difficult, and very difficult) was 95.9%, 90.6%, 87.6%, and 57.1%, respectively (Figure 6). The rule performed well on ROC curve analysis for predicting technical failure (AUC = 0.728).
In the validation set, we used the same prediction rule to stratify procedures into the same degrees of difficulty in achieving technical success. The following success rates were obtained in the different groups of procedures: 1) easy, 96.8%; 2) intermediate, 96.4%; 3) difficult, 71.9%; and 4) very difficult, 58.8%. In ROC curve analysis, the AUC of the validation set was 0.772 (Figure 6).
In the full cohort, fewer CTO procedures with ORA scores ≥3 were attempted in period 2 in comparison with period 1 (3.2% vs. 10.9%, respectively; p < 0.001). ORA score ≥3 was associated with a significant increase in contrast-induced nephropathy prevalence (12.1% vs. 5.4%; p = 0.031) and a nonsignificant increase in in-hospital MACE occurrence (6.1% vs. 3.6%; p = 0.228).
The main findings of the present study can be summarized as follows: 1) despite the increased complexity of CTO lesions attempted, both technical and clinical success rates have gradually improved; 2) although J-CTO score influenced procedural details, its utility in predicting technical success was limited; and 3) the prediction model including age, ostial location, and collateral filling was able to satisfactorily predict technical failure.
10-year experience with CTO PCI
Reports from different interventionalist communities had shown the impact of operator’s experience and case volume on the success of CTO attempts, particularly with the retrograde approach (7,8). In the present study, a technical success rate superior to 90% had been achieved since the fourth year of experience and was maintained thereafter.
In our study, very difficult lesions accounted for fewer than one-third of CTOs attempted in period 1, whereas in period 2, more than half of the lesions had J-CTO scores ≥3. Notably, the success of recanalization for this grade of complexity increased from 84.3% in period 1 to 91.8% in period 2 (p = 0.017). The development of equipment and techniques (14,15) might also explain, beyond expertise, these latter findings.
By contrast, significant decreases in in-hospital MACEs and contrast-induced nephropathy were observed between the early and late periods. Indeed, in period 2, about 90% of patients with CTO were successfully revascularized, with no in-hospital complications. One of the reasons that could also contribute to the improvement in clinical outcomes is better selection of patients. Indeed, patients attempted in period 2 showed fewer comorbidities (except diabetes), better left ventricular ejection fractions, and a lower prevalence of prior revascularization and multivessel disease.
Similarly to Muramatsu et al. (16), retrograde techniques were used in about 30% of CTO cases. Since its introduction, the retrograde approach has greatly enhanced the success rate in complex CTO lesions not amenable to antegrade techniques. In comparison with antegrade procedures, more in-hospital MACEs were observed with retrograde attempts, particularly due to more tamponade. Although tamponade can be easily managed thanks to rapid diagnosis and pericardiocentesis, expertise in managing coronary perforations is mandatory for retrograde CTO operators (17).
According to the EuroCTO club consensus document, at least 300 CTO attempts (and >50 procedures per year) are necessary to acquire expertise in CTO PCI; furthermore, 50 retrograde attempts (25 as second operator and 25 as first operator under supervision) are required before an interventionalist becomes an independent retrograde operator (13). Needless to say, the learning curve for CTO PCI should be a deliberate, stepwise process including proctoring and continuing medical education conferences, with patient safety being the primary concern during skill advancement.
J-CTO Score and the prediction of technical success
The J-CTO score was originally developed to predict the likelihood of successful guidewire crossing within 30 min, not final technical success (10). Recently, in patients included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention), the J-CTO score was strongly associated with final success, showing satisfactory calibration and discrimination (p for Hosmer-Lemeshow test = 0.743, AUC = 0.705) (11). In contrast to Christopoulos et al. (11), in our cohort, J-CTO score demonstrated low calibration and discrimination in predicting technical success of CTO attempts. Such a finding was also reported by Nombela-Franco et al. (12).
In our study, reductions in procedural and fluoroscopy times and contrast load were observed only in lesions with J-CTO scores <3. Indeed, in very difficult lesions, the improvement in success rate was achieved at the expense of more time and contrast. With expertise, a CTO-dedicated operator learns to persist using a methodical approach until a successful outcome is achieved, of course always considering the limitations of dose radiation and contrast. In fact, the higher the J-CTO score, the greater the use of antegrade dissection re-entry techniques and retrograde approaches in order to overcome anatomic difficulties. This suggests that for lesions with high J-CTO scores, early change of crossing strategy should be considered to avoid unnecessary delays predisposing to failure and complications. Therefore, operator experience and use of appropriate recanalization techniques and dedicated soft guidewires might blunt, at least partially, the impact of lesion complexity as assessed by J-CTO score on decreasing technical success.
Ostial location and lack of visibility of a path in the distal vessel have been recognized to considerably affect the ability to successfully cross a CTO (18–20). In our cohort, these 2 angiographic variables independently predicted technical failure. In addition, CTO PCI was less successful in older patients (≥75 years of age), as previously reported (8,9).
Recently, Alessandrino et al. (21) developed the CL score, including both clinical and angiographic score variables (previous coronary artery bypass [+1.5], previous MI [+1], severe lesion calcification [+2], CTO length >20 mm [+1.5], non–left anterior descending coronary artery location [+1], and blunt stump morphology [+1]). This latter score predicted the success of first antegrade CTO attempt and might be applicable at centers where the retrograde or hybrid approach has not yet been implemented. The PROGRESS score developed by Christopoulos et al. (22) and based on 4 angiographic variables has been shown to estimate technical success in CTO PCI performed using the hybrid approach.
In our study, the ORA score, in addition to being simple and easy to remember, demonstrated satisfactory calibration and discrimination for predicting technical failure using both antegrade and retrograde CTO techniques. Including relevant clinical and angiographic parameters, this score can be applied in association with J-CTO score calculation. Although J-CTO score could be useful to assess the complexity of a CTO lesion and to schedule the appropriate recanalization strategies to use, the established new score could be of value for predicting CTO PCI failure. Interestingly in our cohort, ORA score >3 was associated with worse in-hospital outcomes after CTO procedures. Hence, this model could be also helpful to select appropriate CTO PCI candidates and to answer to the question of whether percutaneous revascularization is worthwhile.
First, its retrospective nature might introduce an inevitable case selection bias. Second, all the procedures were performed by a single CTO-dedicated operator; hence, results might not be applicable to the entire population of CTO operators and the elaborated score required to be applied among CTO operators’ community. Nonetheless, reported data cover a 10-year period, which can be associated with different levels of expertise in CTO PCI. Third, to simplify the scoring system, we assigned 1 point for both age category and ostial location and 2 points for collateral filling Rentrop grade <2, according to their relative beta coefficients. Other possibilities might have been used, such as an absolute coefficient for each factor or approximate integral values. Fourth, the definitions used for non–Q-wave MI and contrast-induced nephropathy could underestimate their occurrence. Fifth, data regarding radiation exposure were not reported. Finally, this analysis did not take into consideration the advent of new techniques and CTO-specific medical technology devices during the study period.
With growing expertise and procedural volume, the number of CTO procedures and the success rate have dramatically increased over the years, and more cases were attempted with a retrograde approach. Despite its correlation with lesion complexity, the utility of the J-CTO score in predicting technical success was demonstrated to be limited. The established prediction model including age, ostial location, and collateral filling was strongly associated with technical failure. Further validation of this score in large cohorts of patients attempted by different CTO operators with different levels of expertise will be required to expand its use in CTO interventions.
WHAT IS KNOWN? The interest in CTO PCI has grown exponentially because of important developments in equipment and techniques, with high success rates achieved by dedicated operators and centers. The rational selection of suitable candidates for PCI among patients with CTO might represent an important issue to guarantee higher success and better outcomes.
WHAT IS NEW? We developed a new predictive model (the ORA score) for technical failure of CTO PCI using both antegrade and retrograde techniques. This score includes clinical and angiographic variables.
WHAT IS NEXT? Validation is required among CTO operators. The ORA score might also be applied to select suitable PCI candidates among patients with CTO.
For supplemental figures and tables, please see the online version of this article.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- area under the curve
- confidence interval
- chronic total occlusion
- major adverse cardiac event(s)
- myocardial infarction
- odds ratio
- ostial location, Rentrop grade <2, age ≥75 years
- percutaneous coronary intervention
- receiver-operating characteristic
- Received September 21, 2015.
- Revision received January 13, 2016.
- Accepted January 28, 2016.
- American College of Cardiology Foundation
- ↵Galassi AR, Brilakis ES, Boukhris M, et al. Appropriateness of percutaneous revascularization of coronary chronic total occlusions: an overview. Eur Heart J 2015 Aug 7 [E-pub ahead of print].
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