Impact of the Occlusion Duration on the Performance of J-CTO Score in Predicting Failure of Percutaneous Coronary Intervention for Chronic Total Occlusion

Abstract: Objectives. The present study examined the association between Multicenter CTO Registry in Japan (J-CTO) score in predicting failure of percutaneous coronary intervention (PCI) correlating with the estimated duration of chronic total occlusion (CTO). Background. The J-CTO score does not incorporate estimated duration of the occlusion. Methods. This was an observational retrospective study that involved all consecutive procedures performed at a single tertiary-care cardiology center between January 2009 and December 2014. Results. A total of 174 patients, median age 59.5 years (interquartile range [IQR], 53-65 years), undergoing CTO-PCI were included. The median estimated occlusion duration was 7.5 months (IQR, 4.0-12.0 months). The lesions were classified as easy (score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score ≥3) in 51.1%, 33.9%, 9.2%, and 5.7% of the patients, respectively. Failure rate significantly increased with higher J-CTO score (7.9%, 20.3%, 50.0%, and 70.0% in groups with J-CTO scores of 0, 1, 2, and ≥3, respectively; P<.001). There was no significant difference in success rate according to estimated duration of occlusion (P=.63). Indeed, J-CTO score predicted failure of CTO-PCI independently of the estimated occlusion duration (P=.24). Areas under receiver-operating characteristic curves were computed and it was observed that for each occlusion time period, the discriminatory capacity of the J-CTO score in predicting CTO-PCI failure was good, with a C-statistic >0.70. Conclusion. The estimated duration of occlusion had no influence on the J-CTO score performance in predicting failure of PCI in CTO lesions. The probability of failure was mainly determined by grade of lesion complexity. 

J INVASIVE CARDIOL 2017;29(6):195-201.

Key words: coronary disease, coronary occlusion, angioplasty

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) still remains a challenging procedure for the interventional cardiologist. Nowadays, the significantly enhanced success rates of percutaneous CTO revascularization can be attributed to the introduction of new crossing techniques, equipment, and technologies, along with increasing experience of dedicated operators.^1-3 Furthermore, the successful recanalization of CTO has been shown to reduce angina symptoms,^4,5 decrease anti-angina medication intake, and improve exercise capacity,⁶ left ventricular systolic function,⁷ and long-term survival.⁸ Nevertheless, in North American centers,⁹ only between 6% and 9% of patients were treated percutaneously, and a high proportion of patients with CTOs are still being managed medically or referred for coronary artery bypass graft surgery rather than PCI.^4,10 The inability to cross the lesion with the guidewire is the main reason for PCI failure in CTOs.¹¹ The multicenter Japanese CTO Registry¹² investigators developed the J-CTO score as a scoring system to grade the difficulty in crossing a CTO within 30 minutes and overall success rate.¹³ However, estimated occlusion duration was not considered in the development of the J-CTO score, and previous studies have reported that indeterminate aging or long-duration occlusion were associated with procedure failure.^14-16

The aim of this study was to evaluate the impact of the occlusion duration on the performance of J-CTO score in predicting CTO-PCI failure in a consecutive series of patients.

Methods

Study design and patient population. We examined all consecutive patients who underwent CTO-PCI between January 2009 and December 2014 by experienced high-volume operators at a tertiary cardiology center. Patients who presented with estimated occlusion duration <3 months, Thrombolysis in Myocardial Infarction (TIMI) flow grade >0, and occluded arterial or venous graft lesions were excluded of this study. No angiographic characteristic was regarded as absolute contraindication to CTO recanalization attempt. Hence, the final analysis consisted of 174 patients. The protocol was approved by our Institutional Ethical Committee and conformed to the principles outlined in the Declaration of Helsinki. All patients provided written informed consent.

Baseline, procedural, and hospitalization data were prospectively collected and entered in a dedicated database. For each case, angiographic characteristics were reviewed by two experienced independent interventional cardiologists. All procedures were scheduled (as opposed to ad hoc), 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 CTO artery territory, as demonstrated by functional imaging tests. 

Definitions and analyses. CTOs were defined as 100% coronary artery occlusion, with antegrade TIMI flow grade 0, confirmed or presumed to be ≥3 months old.¹⁷Estimation of the occlusion duration was based on clinical information or comparison with previous angiography. Patients with unchanged ischemic symptoms for at least 3 months or with silent ischemic evidence and coronary angiogram suggesting long duration of occlusion (no contrast staining within the lumen and presence of bridging collateral vessels) were judged as having occlusion duration indeterminate. 

Successful angiographic recanalization (technical success) was defined as restoration of TIMI grade 3 and residual stenosis <30% in the occluded artery. Multivessel disease was defined as stenosis ≥70% in >1 major coronary artery. Retrograde collateral circulation following Rentrop definition¹⁸ was used to calculate the length of the occlusion segment using manual calibration with the catheter tip as a reference. 

The J-CTO score was calculated for each lesion based on length of occluded segment >20 mm; blunt stump at the proximal cap; presence of calcification; bending >45° in the CTO segment; and prior failed attempt, as previously described.¹³ The score was developed giving 1 point for each of these independent predictors when present. The CTO case complexity was further stratified into easy (J-CTO score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score = 3-5). 

Interventional procedures. All patients were pretreated with aspirin and clopidogrel (300 mg loading dose at least 24 h prior to procedure) and both were continued for at least 1 year in successful cases. Patients received an initial bolus of intravenous unfractionated heparin (70-100 IU/kg) and anticoagulation was monitored during the procedure in order to maintain an activated clotting time >250 s. Upstream use of glycoprotein IIb/IIIa inhibitor therapy was avoided for the potential increased risk of bleeding in case of coronary perforation. 

Six to 7 Fr guiding catheters were used. The choice of CTO revascularization strategy was left to the operator’s discretion. When there was suitable visualization of the distal occluded vessel from the opposite coronary artery, bilateral coronary injection was undertaken. The antegrade approach was routinely used with double coronary cannulation and contralateral selective injection in some cases. Several guidewire strategies were used, including the single-wire technique, the parallel-wires technique, and retrograde wiring through collateral vessels. The majority of patients had drug-eluting stent implantation. 

Statistical analysis. Continuous data were reported as median ± interquartile range (IQR) and compared using Kruskal-Wallis test when non-normally distributed. Categorical data were presented as frequencies with percentages and compared using Chi-squared or Fisher’s exact test, as appropriate. A binary logistic regression model was used to predict the likelihood of angiographic PCI failure according to J-CTO score stratified by estimate occlusion duration in three categories: <12 months, ≥12 months, and indeterminate occlusion duration. The variance analysis with Chi-squared test was used to calculate the reduction of goodness of fit for regression models after inclusion of occlusion duration variable in the model. The goodness of fit of the final regression model was evaluated using the Hosmer-Lemeshow (HL) test and the discriminatory power of the model was assessed by the area under the receiver-operating curve (ROC) and the C-index. A two-sided P-value of <.05 was considered statistically significant. Statistical analyses were performed using R package software version 3.12 (The R Foundation for Statistical Computing).

Results

Baseline characteristics. The population of this study consisted of 174 patients with single CTO lesions who had undergone elective PCI. Median age was 59.5 years (range, 53.0-65.8 years), 69.0% were men, 32.2% had type 2 diabetes mellitus, and 17.8% had chronic kidney disease (creatinine clearance <60 mL/min/1.73²). The estimated occlusion duration was known in 126 patients (72.5%) and the median was 7.5 months (IQR, 4.0-12.0 months). Forty-nine patients (28.2%) had estimated occlusion duration ≥12 months and 77 patients (44.3%) had CTO duration <12 months. The remaining 48 patients (27.5%) had indeterminate occlusion duration. Baseline characteristics are summarized in Table 1.

Angiographic characteristics. Table 2 presents a summary of angiographic characteristics obtained from detailed qualitative assessments. PCI was performed mainly in the left anterior descending coronary artery (42.0%) and multivessel disease was present in 43.6% of cases. CTO lesions had median occlusion length of 13.6 mm (IQR, 8.6-18.0 mm) and median target vessel diameter was 2.8 mm (IQR, 2.5-3.2 mm). When grouped according to J-CTO score, the proportion of patients with easy (score = 0), intermediate (score = 1), difficult (score = 2), and very difficult (score ≥3) J-CTO scores was 51.1%, 33.9%, 9.2%, and 5.7%, respectively.

Procedure characteristics. Regarding procedure characteristics, femoral approach (56.3%), 6 Fr vascular sheath (94.3%), and drug-eluting stent (71.8%) were predominantly used. The most common crossing technique was antegrade wire escalation (90.3%), resulting in overall success rate of 81.0%. Unsuccessful wire or balloon crossing was mainly responsible for failed CTO-PCI (70.6%). Detailed procedure characteristics are shown in Table 3. 

J-CTO score and estimated occlusion duration. The median values of estimated occlusion duration for each J-CTO score category were 9.0 months (IQR, 4.5-12.0 months), 6.5 months (IQR, 4.0-13.8 months), 7.0 months (IQR, 5.0-12.0 months), and 6.0 months (IQR, 5.0-12.0 months), respectively (P=.99). Likewise, the proportion of longstanding occlusion duration (≥12 months) for each J-CTO score category was 29.2%, 25.4%, 31.2%, and 30.0%, respectively (P=.86). Therefore, the estimated occlusion duration had no relationship with higher J-CTO score, and longer or indeterminate occlusion duration was not associated with a higher J-CTO score (Figure 1). Similarly, estimated occlusion duration was not associated with any specific angiographic characteristic, regarding the analysis of J-CTO variables separately and stratified by estimated occlusion duration groups (Figure 2). 

In a logistic regression multivariate model, we assessed the independent correlates of technical success. Calcification (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.42; P<.01), occluded segment length ≥20 mm (OR, 1.48; 95% CI, 1.29-1.71; P<.01), and bend >45º (OR, 1.35; 95% CI, 1.07-1.70; P=.01) were identified as significant inverse relationships with success, whereas blunt stump type (OR, 1.06; 95% CI, 0.89-1.15; P=.80) and previous failed PCI (OR, 0.83; 95% CI, 0.51-1.35; P=.85) did not show a significant relationship with it in this cohort (Table 4).

There was a significant association between difficulty level of J-CTO score and final success rate, and CTO complexity was a risk factor for no success in CTO opening (P<.001). However, there was no significant difference in success rate related to occlusion duration (P=.63) (Figure 3). Besides, the J-CTO score has proven to be a strong predictor of CTO-PCI failure independently of the estimated occlusion duration, as shown in Figure 4 (P=.24 for interaction). Figure 5 demonstrates that for each occlusion duration, the discriminatory capacity of the J-CTO score in predicting procedure failure was good, with a C-statistic >0.70. Table 5 shows that the calibration of observed against expected rates of CTO-PCI failure according to J-CTO score were adequate (HL test, P>.05) for all occlusion time groups.

Discussion

In this study, we investigated the impact of the estimated duration of occlusion on the accuracy of J-CTO score in predicting failure of CTO-PCI. This analysis adds considerably to the current knowledge of CTOs, with the main findings of this study as follows: (1) the estimated duration of occlusion in CTO lesions had no correlation with the grade of lesion complexity when analyzed by J-CTO score; (2) procedure success rate was mainly determined by complexity of coronary lesions; (3) longer occlusion duration was not associated with higher CTO-PCI failure rates; and (4) J-CTO score was a strong predictor of CTO-PCI failure irrespective of the estimated occlusion duration.

Histological CTO lesion analyses showed that the duration of occlusion could influence the presence of calcification, inflammation, and neovascularization.¹⁹ Thus, it was expected that lesions with longer duration of occlusion should be associated with greater anatomical complexity and could result in lower CTO-PCI success rates, regarding the increase of lesion organization with deposition of fibrous tissue and calcification, which occurs in the course of time from occlusion.²⁰ However, this was not found in our research. Our study showed that lesions with estimated occlusion duration >12 months or indeterminate were not associated with increased angiographic complexity for performing PCI, and the final success rate was mainly determined by complexity of lesion, analyzed by the J-CTO score.¹³ 

Although previous study results showed that both long and indeterminate time of occlusion were associated with higher incidence of procedure failure,^14-16 in the current cohort, the isolated occlusion duration was not able to predict success in CTO-PCI, which is consistent with more recent studies.^20-22 In addition, in our research, there was no relationship between the occlusion duration and presence of any angiographic variables that confers complexity to the lesion, such as calcification, tortuosity, and length of the occlusive segment.

In the study conducted by Tomasello et al,²⁰ who analyzed more than 300 patients, it was demonstrated that the estimated duration of occlusion did not influence either CTO-PCI success rate or 1-year major adverse cardiovascular event rate. The occlusion duration certainly is not the only determinant of occlusive lesion complexity, and other variables are important, such as individual genetic variations, as well as the control of other clinical factors that could influence atherosclerotic disease progression. The reason for the low frequency of PCI in CTOs is likely determined by the expected lower success rate and higher procedural costs and efforts. Nevertheless, the decision of whether or not to attempt CTO-PCI often depends on angiographic and clinical characteristics, such as timing of occlusion and grade of collateral circulation.²³ 

Nowadays, more than the lesions characteristics, the determinant factors for successful CTO-PCI are skilled and experienced operators. A complete knowledge of CTO-PCI techniques and new materials is the main strategy to improve procedural success from the historically rates of approximately 60% to the levels now routinely quoted by expert operators (80%-90%).^15,23,24 

The J-CTO score, here used to assess the degree of anatomic complexity of the CTO lesion and not only as a predictor of success in crossing the lesion within 30 minutes as originally validated,¹³ remains as a strong global predictor of procedure success in this population, whatsoever the estimated duration of occlusion or even procedure time. Some isolated variables of J-CTO score are routinely associated with higher incidence of PCI failure, such as blunt stump tip.^6,25 However, in more recent analyses, this association did not remain significant toward predicting PCI failure,²⁶ as shown in our study. This phenomenon could be explained by an augmentation in intracoronary ultrasound throughout the last years in order to identify an entry point, or even expanding the use of retrograde technique as an alternative for CTO cases presenting with blunt stump tip, although in our study the practice of these techniques has been very low.

Likewise, lesions with previous attempt also are no longer associated with angiographic failure in retry PCI-CTO.²⁶ Nevertheless, after comparing the CTO-PCI success rates in two time intervals (2003-2008 vs 2008-2012) in 483 patients according to the degree of lesion complexity, Syrseloudis et al²⁷ showed that both lesion complexity assessed by J-CTO score and the time interval were independent predictors of angiographic success rate.

Therefore, the J-CTO score still remains a simple, quick, and accurate tool for the interventional cardiologist to decide whether or not to perform PCI through a CTO lesion. In addition, the estimated duration of occlusion is not a good determinant of complexity or a predictor of  procedural success.

Study limitations. The present analysis has some limitations. This study was an observational and retrospective analysis, and as such, is subject to inherent limitations. Moreover, it only reflected the experience of a single institution that has invested significant resources to develop expertise in CTO-PCI, with dedicated operators to these complex lesions, and may not apply to less experienced operators and centers. Also, the lack of trustworthy information about symptoms or the absence of previous angiographic imaging in some cases could lead to misinterpretation of occlusion duration. Finally, the relatively small sample size could diminish the study’s findings and does not allow us to draw a final conclusion, but should be assessed as “hypothesis generating” and encourage the idea of developing randomized clinical trials in this field.

Conclusion

The estimated duration of occlusion had no influence on the J-CTO score performance in predicting failure of PCI in CTO lesions, and the probability of procedure failure was mainly determined by grade of lesion complexity. Percutaneous treatment should be considered a reliable strategy for CTO lesions regardless of occlusion duration.

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From the Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted January 28, 2017, accepted February 8, 2017.

Address for correspondence: Antonio de Castro-Filho, MD, Dante Pazzanese Av., n. 500, 04012-909, Sao Paulo, Brazil. Email: afilhocastro@gmail.com