Chronic total occlusion (CTO) is a common finding in. Angioplasty

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1 Angioplasty Validation of the J-Chronic Total Occlusion Score for Chronic Total Occlusion Percutaneous Coronary Intervention in an Independent Contemporary Cohort Luis Nombela-Franco, MD; Marina Urena, MD; Miguel Jerez-Valero, MD; Can Manh Nguyen, MD; Henrique Barbosa Ribeiro, MD; Yoann Bataille, MD; Josep Rodés-Cabau, MD; Stéphane Rinfret, MD, SM Background Chronic total occlusion (CTO) recanalization is a complex and technically challenging procedure. The J-CTO score has been proposed to stratify case complexity and procedural success rates. However, the score has never been tested outside the setting of the original study. Moreover, its predictive value when using a hybrid antegrade or retrograde approach is unknown. We investigated the performance of the J-CTO score for predicting procedure complexity and success in an independent contemporary cohort. Methods and Results A total of 209 consecutive patients who underwent CTO recanalization by a high-volume operator were included. Clinical and angiographic data were prospectively collected. The J-CTO score was applied for each patient, and discrimination and calibration were evaluated in the whole cohort, and according to the approach (antegrade 47% and retrograde 53%). Clinical and angiographic differences were noted between the original and studied cohort. The mean J-CTO score was 2.18±1.26, and successful guidewire crossing within 30 minutes and final angiographic success were 44.5% and 90.4%, respectively. The J-CTO score demonstrated good discrimination (c statistic, >0.70) and calibration (Hosmer Lemeshow P>0.1) in the whole cohort and for antegrade and retrograde approaches. However, the final success rate was not associated with the J-CTO score. Conclusions In this independent cohort, the J-CTO score showed good discriminatory and calibration capacity for guidewire CTO crossing within 30 minutes but it does not for final success rate. The J-CTO score helps to predict complexity of CTO recanalization, and the simplicity of the score supports the widespread use as a clinical tool. (Circ Cardiovasc Interv. 2013;6: ) Key Words: chronic disease coronary occlusion percutaneous coronary intervention Chronic total occlusion (CTO) is a common finding in patients with coronary artery disease 1 and is associated with poorer outcomes compared with patients with ischemia with non-cto disease. 2 5 Although better clinical outcomes have been associated with successful recanalization in observational studies, 6 8 CTO percutaneous coronary intervention (PCI) remains a major challenge for many interventional cardiologists, and developing new strategies to approach CTO is important for the field. Angiographic CTO lesion characteristics are predictive of success rate and procedure time The multicenter Japanese CTO Registry 12 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 Thus, it might be a valuable tool for some operators dealing with the challenge of patient selection for CTO PCI and for schedule management. However, the J-CTO score has never been tested outside the setting of the original study, and its validity has not been established in a non-japanese population. Moreover, the retrograde approach is an established procedure, which improves the success rate, 14 but the proportion of patients with retrograde approach in the original Japanese registry was relatively low. Hence, the predictive value of the J-CTO score when using modern hybrid antegrade and retrograde approaches is unknown. The purpose of the study was therefore to (1) evaluate the performance of the J-CTO score for predicting procedure complexity defined as guidewire CTO crossing within 30 minutes and final success rate in an independent CTO cohort and (2) to assess its performance for antegrade and retrograde approaches. Received April 20, 2013; accepted October 10, From the Multidisciplinary Department of Cardiology, Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart & Lung Institute), Laval University, Quebec City, Quebec, Canada. Correspondence to Stéphane Rinfret, MD, SM, Interventional Cardiology and Clinical Research, Multidisciplinary Department of Cardiology, Institut universitaire de cardiologie et de pneumologie de Québec (Quebec Heart & Lung Institute), 2725 Chemin Ste-Foy, Quebec City, G1V 4G5 Quebec, Canada. Stephane.Rinfret@criucpq.ulaval.ca 2013 American Heart Association, Inc. Circ Cardiovasc Interv is available at DOI: /CIRCINTERVENTIONS

2 636 Circ Cardiovasc Interv December 2013 What Is Known Chronic total occlusion (CTO) percutaneous coronary intervention remains a difficult procedure associated with higher failure rates than angioplasty for subtotal lesions. The J-CTO score, derived from a large registry, stratifies case complexity and the likelihood of success. What the Study Adds However, the score had not been validated in an independent cohort. This study indicates that the J-chronic total occlusion score is valid and useful to predict the time required to cross the chronic total occlusion, the total procedure time, and radiation dose and contrast use. However, it was not helpful to predict success rate, using hybrid antegrade, retrograde, and reentry techniques. Methods Study Population and CTO Procedures Between January 2010 and December 2012, a total of 245 consecutive CTO PCI were performed by a single operator (S.R.). Of these, 36 (14.7%) patients were performed outside our institution and were not Table 1. Patient and Lesion Baseline Characteristics of the Study Population and Differences With the Derivation J-CTO Score Population Variables Study Population (Canadian; n=209) J-CTO Population (Japanese; n=329) Age, y (median) 67 (60 74) Age 75 y 48 (23.0) 87 (26.4) Men 171 (81.8) 263 (79.9) BMI, kg/m ±5.3 Previous PCI 137 (65.6) 141 (42.9) Previous CABG 59 (28.2) 28 (8.5) EF, % 55.3±11.1 EF (9.1) 46 (14.0) Heart failure 19 (9.1) 41 (12.5) Previous MI 117 (56.0) 151 (45.9) Multivessel disease 110 (52.6) 214 (65.1) egfr, ml/min 76.7 ( ) Hemodialysis 1 (0.5) 14 (4.3) Hypertension 146 (69.9) 243 (73.9) Dyslipidemia 185 (88.5) 171 (52.0) Smoking 55 (26.3) 62 (18.8) Diabetes mellitus 69 (33) 136 (41.3) Family history of CAD 72 (34.4) 43 (13.1) Data are presented as mean±sd, n (%), or median (Q1 Q3). BMI indicates body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; CTO, chronic total occlusion; EF, ejection fraction; egfr, estimated glomerular filtration rate; MI, myocardial infarction; and PCI, percutaneous coronary intervention. available for angiographic analysis. Hence, the final study population consisted of 209 patients, all patients referred for CTO PCI, without angiographic exclusion criteria. Baseline, procedural and hospitalization data were prospectively collected and entered in a dedicated database. Our institutional review committee approved prospective data collection as part of the Recherche Évaluative en Cardiologie InTervenionnelle (RÉCIT) registry, and subjects provided signed informed consent. A CTO was defined as an obstruction of a coronary artery with anterograde thrombolysis in myocardial infarction flow grade 0 that was confirmed or presumed to be 3 months old. 11 The duration of the CTO was estimated by clinical information or the results of previous angiography. Successful angiographic recanalization was defined as a restoration of thrombolysis in myocardial infarction flow grade 3 and residual stenosis <30% in the occluded artery. Successful procedure was defined as successful angiographic recanalization and no in-hospital major adverse cardiovascular event including death, stroke, major vascular complication, tamponade requiring pericardial drainage, or need for urgent surgery. Contrast-induced nephropathy was also recorded and defined as an increase in creatinine by 0.5 mg/dl or >25% of the baseline value. 15 Neither occluded arterial graft nor vein graft lesions were considered for this study. When possible, arterial access was established via bilateral radial approach (right radial for the left main catheter and left radial for the right coronary artery catheter to optimize support), and 6F catheters were used primarily. 16 The preferred guiding catheter curves were Amplatz left (AL) 0.75 for the right coronary and extra back-up (XB) 3.5 for the left. FinecrossMG (Terumo, Tokyo, Japan) and Corsair (Asahi Intecc, Nagoya, Japan) microcatheters were generally used for antegrade and retrograde approaches, respectively. Dual injection was used routinely when contralateral collaterals were present. The approach to the CTO was based on the anatomy following Table 2. Variables Angiographic and Procedural Characteristics Study Population (Canadian; n=209) J-CTO Population (Japanese; n=329) Target lesion LAD 43 (20.6) 122 (37.1) LCx 39 (18.7) 68 (20.7) LM 2 (1.0) 1 (0.3) RCA 124 (59.3) 138 (42.0) Previously failed attempt 64 (30.6) 38 (11.6) Ostial location 36 (17.2) 35 (10.6) Side branches 114 (54.5) 271 (82.4) Blunt stump at entry site 110 (52.6) 133 (40.4) Calcifications 90 (43.1) 180 (54.7) Bridging collaterals 81 (38.8) 77 (23.4) Bending >45 92 (44.0) 143 (43.5) Occlusion length, mm 26.2± ± (47.4) 72 (21.9) Retrograde collateral (grade=3) 148 (70.8) 277 (84.2) Successful guidewire crossing 92 (44.0) 160 (48.6) in <30 min J-CTO score Easy (J-CTO=0) 21 (10.0) 65 (19.8) Intermediate (J-CTO=1) 45 (21.5) 82 (24.9) Difficult (J-CTO=2) 57 (27.3) 92 (28.0) Very difficult (J-CTO 3) 86 (41.1) 90 (27.4) Retrograde approach 111 (53.1) 136 (25.8)* CTO indicates chronic total occlusion; LAD, left anterior descending artery; LCx, left circumflex; LM, left main; and RCA, right coronary artery. *Entire cohort of the J-CTO registry (n=528).

3 Nombela-Franco et al Validation of the J-CTO Score 637 Table 3. Baseline Characteristics According to J-CTO Score Categories Variables J-CTO=0 (n=21) J-CTO=1 (n=45) J-CTO=2 (n=57) J-CTO 3 (n=86) P Value Age, y (median) 71 (67 77) 66 (61 73) 67 (57 78) 66 (58 72) Men 17 (81.0) 36 (80.0) 50 (87.7) 68 (79.1) BMI, kg/m ± ± ± ± Previous PCI 11 (52.4) 27 (60.0) 39 (68.4) 60 (69.8) Previous CABG 6 (28.6) 9 (20.0) 13 (22.8) 31 (36.0) EF, % 56.5± ± ± ± Heart failure 1 (4.8) 1 (2.22) 6 (10.5) 11 (12.8) Previous MI 10 (45.6) 22 (48.9) 33 (57.9) 52 (60.5) Multivessel disease 13 (61.9) 22 (48.9) 31 (54.4) 44 (51.2) egfr, ml/min 72.4 ( ) 86.1 ( ) 77.0 ( ) 75.4 ( ) Hemodialysis (1.2) Hypertension 15 (71.4) 33 (73.3) 39 (68.4) 59 (68.6) Dyslipidemia 19 (90.5) 40 (88.9) 49 (86.0) 77 (89.5) Smoking 4 (19.0) 10 (22.2) 12 (21.1) 29 (33.7) Diabetes mellitus 4 (19.0) 15 (33.3) 14 (24.6) 36 (41.9) Family history of CAD 7 (33.3) 16 (35.6) 14 (24.6) 35 (40.7) Data are presented as mean±sd, n (%), or median (Q1 Q3). BMI indicates body mass index; CABG, coronary artery bypass graft; CAD, coronary artery disease; CTO, chronic total occlusion; EF, ejection fraction; egfr, estimated glomerular filtration rate; MI, myocardial infarction; and PCI, percutaneous coronary intervention. a previously described algorithm. 17 Briefly, antegrade approach was initially attempted for short lesions (<20 mm) with clear proximal cap and good distal vessel target using a wire escalation strategy (Fielder XT Asahi Intecc; Pilot 50, Abbott Vascular; Pilot 200 Abbott Vascular or Confianza Pro 12, Asahi Intecc, according to the lesion characteristics). 16 Antegrade dissection and reentry techniques using dedicated devices were used for longer lesions and optimal distal zone of reentry without significant side-branches. 18 Other complex lesions with ambiguous proximal caps and poor distal target were attempted by retrograde approach. A soft guidewire (Fielder FC or more recently Sion, Asahi Intecc) was used to cross the collaterals, and distal tip injections were not typically performed. Once the microcatheter reached the distal cap, a true-to-true lumen crossing technique with externalization of the wire was attempted. When entering in the subintimal space or with long lesion, knuckled wires were used to reach the proximal cap of the occlusion followed by reverse-cart techniques. 14 The occluded segment was always stented with drug-eluting stents, and postdilation was performed to optimize stent expansion and apposition. The J-CTO score was prospectively calculated in all the patients after the publication of the original study (February 2011) and retrospectively in patients who underwent PCI before the publication but was not used to turn down patients for CTO PCI based on anatomy. Time to cross was defined as in the original index publication, using the wire working time, and confirmation of wire true distal lumen positioning by angiography and catheterization report review. The primary end point was defined as time to cross within 30 minutes. The secondary end points were final angiographic and procedural successes. The J-CTO Score This score was derived from the Japanese CTO registry from the analysis of 500 native CTO lesions. 13 Defining case complexity by Figure 1. Successful guidewire crossing within 30 minutes according to the J-chronic total occlusion (CTO) score, in the entire cohort (P for linear trend <0.001) and stratified by antegrade (P for linear trend=0.002) and retrograde (P for linear trend <0.001) approaches. GW indicates guidewire.

4 638 Circ Cardiovasc Interv December 2013 Figure 2. A, Receiver-operating characteristics (ROC) curve for probability of guidewire crossing success within 30 minutes and (B) ROC curve for global success rate. CI indicates confidence interval; CTO, chronic total occlusion; and PCI, percutaneous coronary intervention. guidewire CTO crossing within 30 minutes and procedure success, 5 independent predictors were found: (1) calcification; (2) bending >45 in the CTO segment; (3) blunt proximal cap; (4) length of occluded segment >20 mm; and (5) previously failed attempt. A score (J-CTO) 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). Statistical Analysis Binary variables were expressed as percentages, and continuous variables were expressed as mean values and SD or as median values and quartiles (Q1 Q3), based on data distribution assessment performed by the Kolmogorov Smirnov test. Categorical variables were compared using the χ 2 test, and continuous variables were compared using 1-way ANOVA or Kruskal Wallis test to determine differences between mean or median values among the J-CTO categories, respectively. Trend test was performed. The association between a <30-minute guidewire manipulation duration (dichotomized as in the original index description) required to cross the lesion and the J-CTO score (predictor variable) was assessed using logistic regression. The goodness-of-fit of the logistic model was examined using the Hosmer and Lemeshow (HL) goodness-of-fit statistic. 19 The HL statistic tests the actual versus the predicted responses; theoretically, the observed and expected counts should be close. Based on the χ 2 distribution, an HL statistic with a P value >0.05 was considered a good fit. The discriminatory power of the logistic model was assessed by the area under the receiver-operating characteristics (ROC) curve or the C-index. 20 A model with perfect discriminative ability has a C-index of 1.0; an index of 0.5 provides no better discrimination than chance. Models with area under the ROC curve >0.7 are considered to have a meaningful discriminatory ability. The model was also repeated separately for procedures performed in an earlier (first half; n=104) and a later (second half; n=105) period, involving antegrade or retrograde approaches and dissection-reentry techniques. All analyses were performed using the statistical package SAS (version 9.2; SAS Institute Inc, Cary, NC) considering significant results with P values <0.05. Table 4. Observed and Predicted Rates (95% CI) for Guidewire Crossing Within 30 Minutes in the Entire Cohort and Stratified by Approach and J-CTO Scale Variables n Observed Predicted Hosmer Lemeshow % 95% CI % 95% CI χ 2 P Value Total Easy (J-CTO=0) Intermediate (J-CTO=1) Difficult (J-CTO=2) Very difficult (J-CTO 3) Antegrade Easy (J-CTO=0) Intermediate (J-CTO=1) Difficult (J-CTO=2) Very difficult (J-CTO 3) Retrograde Easy (J-CTO=0) Intermediate (J-CTO=1) Difficult (J-CTO=2) Very difficult (J-CTO 3) CI indicates confidence interval; and CTO, chronic total occlusion.

5 Nombela-Franco et al Validation of the J-CTO Score 639 Table 5. Univariate and Multivariate Analyses of Successful Guidewire Crossing Within 30 Minutes Variables Univariate Analysis Multivariate Analysis* OR (95% CI) P Value OR (95% CI) P Value Blunt stump type 0.21 ( ) ( ) Occlusion length 20 mm 0.22 ( ) ( ) Calcification 0.36 ( ) ( ) Bending 0.51 ( ) ( ) Previous failed lesion 0.82 ( ) ( ) CI indicates confidence interval; and OR, odds ratio. *Adjusted for age, diabetes mellitus, and renal function. Results Baseline Characteristics Baseline clinical and angiographic characteristics are shown in Tables 1 and 2, respectively. Compared with the Japanese population, patients in our cohort showed an overall different risk profile. The prevalence of dyslipidemia, smoking, family history of coronary artery disease, previous myocardial infarction, and previous percutaneous and surgical revascularization was higher among Canadian patients. The Japanese patients were more likely to have diabetes mellitus and chronic renal failure on hemodialysis (Table 1). There were also relevant angiographic differences in CTO lesion characteristics, leading to a higher J-CTO score in the Canadian cohort ( 3: 41.1% of lesions in Canadian versus 27.4% in Japanese patients; Table 2). Although the Japanese patients had more calcified lesion and side branches in the proximal cap, the Canadian group had longer lesions with more bridging collaterals, blunt stump at CTO entry, unsuccessful previous attempt, and worse collateral distal flow. The proportion of patients with an easy (score=0), intermediate (score=1), difficult (score=2), and very difficult (score 3) J-CTO score was 10.1%, 21.5%, 27.3%, and 41.1%, respectively. Baseline characteristics of the study population were similar among J-CTO score categories (Table 3). A total of 92 patients (44.0%) achieved the primary end point of lesion crossing within 30 minutes of guidewire working time. Figure 1 shows the decreasing rates of guidewire crossing within 30 minutes as a function of CTO complexity (P for linear trend <0.001). Discrimination and Calibration of the J-CTO Score The discriminatory capacity of the model in our cohort was good overall with a c statistic of (95% confidence interval [CI], ; P<0.001; Figure 2A). Calibration of observed against expected rates for guidewire crossing within 30 minutes was adequate for the global population (Table 4), as shown by the HL test (HL=7.70; P=0.464). Each of the component variables of the J-CTO score, with the exception of previous failed lesion, had significant univariate association with successful guidewire crossing within 30 minutes (Table 5). Blunt stump at the proximal cap, occlusion length 20 mm, and calcification were also independent predictors in the multivariate analysis in our adjusted model. The proportion of patients with very difficult lesion (J-CTO score 3) was similar for the early and late period (39.4% versus 42.9%; P=0.614). The discriminatory capacity of the model performed well for both the first half (c statistic, 0.767; 95% CI, ; P=0.001; HL=6.48; P=0.593) and the second half (c statistic 0.776; 95% CI, ; P=0.001; HL=2.88; P=0.941) of the period (P=0.890 for comparison of both ROC curves). J-CTO Score and Hybrid Approach A total of 111 (53.1%) CTO PCIs were performed involving a retrograde approach. The J-CTO score was significantly higher when the retrograde approach was required ( 3: 58.6% for retrograde versus 21.4% for antegrade; P=0.001). Consequently, the global proportion of patients with successful Figure 3. A, Receiver-operating characteristics (ROC) curve for probability of guidewire crossing success within 30 minutes according to the approach and (B) revascularization technique. Hanley and McNei test for ROC curve comparison, P=0.816 and P=0.780, respectively. CI indicates confidence interval.

6 640 Circ Cardiovasc Interv December 2013 Table 6. Complexity of the Procedure According to the J-CTO Score J-CTO Score P Value* Contrast amount, ml 175 ( ) 270 ( ) 223 ( ) 320 ( ) Guidewire working time, min 8 (4 14) 24 (9 45) 30 (10 49) 69 (33 118) Fluoroscopy time, min 24 (20 32)# 38 (25 61) 46 (31 72) 84 (48 109)** Radiation dose, µgy/cm ( ) ( ) ( ) ( ) Total procedure time, min 70 (51 84) 100 (74 137) 120 (86 172) 185 ( ) CTO indicates chronic total occlusion. *Jonckheere trend test. Pairwise comparison adjusted by Bonferroni correction: P<0.01 vs J-CTO score 0 and 2, P<0.05 vs J-CTO score 1 and 2; P<0.01 vs J-CTO score 0, 1 and 2; #P<0.01 vs J-CTO score 2; **P<0.01 vs J-CTO score 0, 1, and 2; P<0.01 vs J-CTO score 0, 1, and 2; P<0.01 vs J-CTO score 2; P<0.01 vs J-CTO score 0, 1, and 2. guidewire crossing within 30 minutes was significantly lower in this group compared with patients treated with an antegrade approach (22.3% versus 76.9%; P<0.001). For each J-CTO score strata, the primary end point was achieved more frequently with the antegrade approach (Figure 1). The model performed equally well for patients treated with a retrograde approach (c statistic 0.727; 95% CI, ; P=0.001) compared with those with an exclusive antegrade approach (c statistic, 0.708; 95% CI, ; P=0.001), P=0.816 for comparison of both ROC curves (Figure 3A). As shown in Table 4, the goodness-of-fit test showed optimal calibration in both approaches (P value>0.1 and χ 2 <20). Also, a total of 93 (44%) patients required a dissection-reentry technique (either retrograde or antegrade). The score again showed good discrimination for the true-to-true lumen and the dissection-reentry techniques, P=0.780 for comparison of both curves (Figure 3B). J-CTO Score, Procedure Complexity, and Final Success The CTO complexity as assessed with the J-CTO score was associated with contrast load, radiation dose, time to cross, fluoroscopic time, and procedure time (Jonckheere trend test P<0.001, for all comparison; Table 6). Successful angiographic recanalization was achieved in 189 (90.4%) patients (89.4% in the first half versus 91.4% in the second half of the cohort; P=0.622). The differences in success rate among J-CTO score categories did not reach statistical significance (P=0.290), with success rates >87% in all 4 groups (Figure 4). The area under ROC curves for final angiographic success was (95% CI, ; P=0.136; Figure 2B), confirming the inability of the J-CTO score to predict final angiographic success in this cohort treated with a hybrid approach. The final angiographic success rate was high with both approaches (antegrade 92.9% versus 88.3%; P=0.263; Figure 5). However, the median successful guidewire manipulation time was significantly shorter with the antegrade compared with the retrograde approach (13, Q1 Q minutes versus 57, Q1 Q minutes; P=0.001). In-hospital major adverse cardiovascular event occurred in 4 (1.91%) patients, leading to a procedural success rate of 187 (89.5%) with ROC curve of 0.40 (95% CI, ; P=0.113). The in-hospital complications of the studied population and the individual J-CTO score of these patients are shown in Table 7. Discussion This study validated the J-CTO score in an independent and unselected contemporary CTO PCI cohort. Our results Figure 4. Final technical success of chronic total occlusion (CTO) revascularization according to the J-CTO score in the entire cohort, with guidewire manipulation time required for successful guidewire crossing superimposed in bar graphs, stratified into 4 time categories. GW indicates guidewire.

7 Nombela-Franco et al Validation of the J-CTO Score 641 Figure 5. Technical success rates according to the approach with guidewire manipulation time required for successful guidewire crossing superimposed in bar graphs, stratified into 4 time categories. CTO indicates chronic total occlusion; and GW, guidewire. demonstrated that the J-CTO score had excellent discriminative capacity and calibration for predicting successful guidewire crossing within 30 minutes. However, using a hybrid antegrade and retrograde approach and use of dissectionreentry techniques, the overall angiographic recanalization success rate was not affected by the score. In addition, the discrimination power was similar for pure antegrade and retrograde approaches, but there were significant differences in the guidewire manipulation time between both approaches. A careful evaluation of the lesion complexity is essential before attempting CTO recanalization both for experienced and nonexperienced CTO PCI operators. The J-CTO score has been proposed to assess the complexity of the expected procedure, not only as a time assessment tool, but also to predict success rate. Validation of stratification models in a purely external cohort in which it is to be applied is epidemiologically advisable. Our results confirm that the J-CTO score is a useful tool to stratify CTO PCI complexity in a geographically and ethnically distinct CTO population. Moreover, the accuracy of the score is not affected by the current contemporary hybrid techniques and the presence of clinical and angiographic differences between both cohorts, which support its Table 7. In-Hospital Complication Rate and Individual Patient J-CTO Score Complication Rate, n (%) J-CTO Score Death 2 (0.96) 5, 2 Stroke 2 (0.96) 5, 4 Major perforation requiring 2 (0.96) 3, 5 pericardial drainage Need for urgent surgery 1 (0.48) 3 MACE 4 (1.91) 5, 4, 2 Contrast-induced nephropathy 2 (0.96) 3, 2 Need for dialysis 0 (0) Major vascular complication 0 (0) MACE: combined incidence of death, stroke, major perforation requiring pericardial drainage or need for urgent surgery. CTO indicates chronic total occlusion; and MACE, major adverse cardiovascular event. widespread use. In our multivariate analysis, 3 variables of the score were independent predictors of the end point, and the good performance of the score in Japanese validation cohort (c statistic, 0.76) 13 was maintained and comparable in our independent cohort (c statistic, 0.77). This reproducibility of the analysis in a different population supports its robustness. Other parameters of procedure complexity, such as radiation, amount of contrast, and procedure time, were also associated with J-CTO scores. Furthermore, our results demonstrate the broad applicability of the J-CTO score regardless of the selected strategy (antegrade versus retrograde) and use of dissection-reentry techniques. Although a true-to-true lumen recanalization technique might be preferable because of lower reocclusion rates, 21 such a technique is often impossible to achieve when tackling long lesions, where dissection-reentry seems the only method associated with good success and low complication rates. It is worthwhile to note that the retrograde approach was associated with higher guidewire manipulation time in our cohort; however, retrograde was used in cases with substantially higher J-CTO score where an antegrade-only technique was not advisable. 17 Although the success rate in the very difficult J-CTO strata was 73.3% in the Japanese cohort, the J-CTO score was unable to predict final angiographic success rate in our cohort. Syrseloudis et al 22 showed in a series with a longer inclusion period that the J-CTO score was predictive of successful recanalization. Again, the success rate was lower than in our cohort, and the current techniques and dedicated CTO devices were only used in the most recent period. We think that our findings are novel and reassuring, suggesting that a more liberal use of hybrid antegrade and retrograde approaches and dissection-reentry technique overcome the impact of the complexity on success rate. Even high J-CTO scores should not discourage experienced and dedicated CTO operators to attempt the recanalization. Nevertheless, the J-CTO score remains extremely useful to predict procedure time, contrast load, and radiation, all variables to paramount importance in planning CTO PCI. Although procedural success rate of CTO PCI is increasing in recent

8 642 Circ Cardiovasc Interv December 2013 years, and major in-hospital complications are relatively low ( 1.0% 2.0%), rates nonetheless continue to be higher than for non-cto PCI. 23,24 J-CTO score could help the physician to predict complexity, which is usually related with higher complications rates. With this validation, we think the J-CTO score can clearly assist interventional cardiologists (not only CTO PCI operators) in the treatment decision process. Occlusions with low J-CTO scores could be attempted using simple antegrade-only techniques by lower-volume or in-training CTO operators in standard facilities. However, CTOs with higher J-CTO scores should be referred to a high-volume CTO operator proficient with the hybrid approach. 25 Finally, in dedicated CTO PCI programs, the J-CTO can serve to plan the CTO PCI day schedule, to optimize case number, and to reduce the risk of subsequent case cancelation. Limitations A few study limitations warrant discussion. First, the validation has been performed in a single center series, so applicability of the score in other population has to be confirmed in future studies to prove its generalizability. Also, this is a highvolume operator series, so we could not test the accuracy of the score in lower-volume centers or for lower-volume operators. Therefore, the study findings apply largely, if not exclusively, to operators and programs who can master the hybrid CTO PCI approach with all modern techniques and tools. However, the Japanese CTO registry also involved mainly dedicated high-volume operators, so our results are consistent with respect to the experience of operators. Although the discriminatory capacity of the score was good for the first period of our CTO program, suggesting that it could be applied to beginner operators, futures studies will be needed to determinate the use of the J-CTO score when the PCI is performed by a low-volume operator or using antegrade-only approaches. The J-CTO score was calculated retrospectively in half of the patients, but no differences were observed in the J-CTO score among the patients calculated retrospectively and prospectively (data not shown). It is possible that the lack of prediction of success with the J-CTO score is because of limited sample size. However, we can at least conclude that it should not discourage any attempt by hybrid operators, with a success rate >87% in the worse complex cases. In addition, the discriminatory capacity of the score for in-hospital complications could unfortunately not be assessed because of the small sample size. Finally, no independent core-laboratory was used to the angiographic analysis, although we think it is unlikely that the global findings would have been any different. In conclusion, this study provides a full evaluation of the J-CTO score model in an independent data set representing a contemporary interventional management of CTOs. Even in the presence of substantial differences in clinical and angiographic features with the original derivation cohort, the J-CTO score showed good discriminatory and calibration capacity for guidewire CTO crossing within 30 minutes among antegrade and retrograde approaches but did not predict the final success rate. The simplicity of the score supports its widespread use as a routinely clinically applicable tool. Sources of Funding Dr Nombela-Franco received funding via a research grant from the Fundación Mutua Madrileña (Spain). Dr Jerez-Valero received funding via a grant (Staff/MIR2012/13) from the Colleges of Physicians of Toledo (Spain). Dr Ribeiro is supported by a research PhD grant from CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico Brasil. Disclosures Dr Rinfret is consultant for Boston Scientific and received research funding from Medtronic and Abbott Vascular Canada. The other authors report no conflicts. References 1. Fefer P, Knudtson ML, Cheema AN, Galbraith PD, Osherov AB, Yalonetsky S, Gannot S, Samuel M, Weisbrod M, Bierstone D, Sparkes JD, Wright GA, Strauss BH. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012;59: Claessen BE, van der Schaaf RJ, Verouden NJ, Stegenga NK, Engstrom AE, Sjauw KD, Kikkert WJ, Vis MM, Baan J Jr, Koch KT, de Winter RJ, Tijssen JG, Piek JJ, Henriques JP. Evaluation of the effect of a concurrent chronic total occlusion on long-term mortality and left ventricular function in patients after primary percutaneous coronary intervention. JACC Cardiovasc Interv. 2009;2: Godino C, Bassanelli G, Economou FI, Takagi K, Ancona M, Galaverna S, Mangieri A, Magni V, Latib A, Chieffo A, Carlino M, Montorfano M, Cappelletti A, Margonato A, Colombo A. Predictors of cardiac death in patients with coronary chronic total occlusion not revascularized by PCI. Int J Cardiol. 2013;168: Claessen BE, Dangas GD, Weisz G, Witzenbichler B, Guagliumi G, Möckel M, Brener SJ, Xu K, Henriques JP, Mehran R, Stone GW. Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial. Eur Heart J. 2012;33: Nombela-Franco L, Mitroi CD, Fernández-Lozano I, García-Touchard A, Toquero J, Castro-Urda V, Fernández-Diaz JA, Perez-Pereira E, Beltrán- Correas P, Segovia J, Werner GS, Javier G, Luis AP. Ventricular arrhythmias among implantable cardioverter-defibrillator recipients for primary prevention: impact of chronic total coronary occlusion (VACTO Primary Study). Circ Arrhythm Electrophysiol. 2012;5: Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. Am Heart J. 2010;160: Mehran R, Claessen BE, Godino C, Dangas GD, Obunai K, Kanwal S, Carlino M, Henriques JP, Di Mario C, Kim YH, Park SJ, Stone GW, Leon MB, Moses JW, Colombo A; Multinational Chronic Total Occlusion Registry. Long-term outcome of percutaneous coronary intervention for chronic total occlusions. JACC Cardiovasc Interv. 2011;4: Jones DA, Weerackody R, Rathod K, Behar J, Gallagher S, Knight CJ, Kapur A, Jain AK, Rothman MT, Thompson CA, Mathur A, Wragg A, Smith EJ. Successful recanalization of chronic total occlusions is associated with improved long-term survival. JACC Cardiovasc Interv. 2012;5: García-García HM, van Mieghem CA, Gonzalo N, Meijboom WB, Weustink AC, Onuma Y, Mollet NR, Schultz CJ, Meliga E, van der Ent M, Sianos G, Goedhart D, den Boer A, de Feyter P, Serruys PW. Computed tomography in total coronary occlusions (CTTO registry): radiation exposure and predictors of successful percutaneous intervention. EuroIntervention. 2009;4: Suzuki T, Hosokawa H, Yokoya K, Kojima A, Kinoshita Y, Miyata S, Suzumura H, Kawajiri K, Suzuki T. Time-dependent morphologic characteristics in angiographic chronic total coronary occlusions. Am J Cardiol. 2001;88:167 9, A Sianos G, Werner GS, Galassi AR, Papafaklis MI, Escaned J, Hildick-Smith D, Christiansen EH, Gershlick A, Carlino M, Karlas A, Konstantinidis NV, Tomasello SD, Di Mario C, Reifart N; EuroCTO Club. Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention. 2012;8: Morino Y, Kimura T, Hayashi Y, Muramatsu T, Ochiai M, Noguchi Y, Kato K, Shibata Y, Hiasa Y, Doi O, Yamashita T, Morimoto T, Abe M, Hinohara T, Mitsudo K; J-CTO Registry Investigators. In-hospital outcomes of

9 Nombela-Franco et al Validation of the J-CTO Score 643 contemporary percutaneous coronary intervention in patients with chronic total occlusion insights from the J-CTO Registry (Multicenter CTO Registry in Japan). JACC Cardiovasc Interv. 2010;3: Morino Y, Abe M, Morimoto T, Kimura T, Hayashi Y, Muramatsu T, Ochiai M, Noguchi Y, Kato K, Shibata Y, Hiasa Y, Doi O, Yamashita T, Hinohara T, Tanaka H, Mitsudo K; J-CTO Registry Investigators. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4: Joyal D, Thompson CA, Grantham JA, Buller CE, Rinfret S. The retrograde technique for recanalization of chronic total occlusions: a step-bystep approach. JACC Cardiovasc Interv. 2012;5: Tepel M, Aspelin P, Lameire N. Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation. 2006;113: Rinfret S, Joyal D, Nguyen CM, Bagur R, Hui W, Leung R, Larose E, Love MP, Mansour S. Retrograde recanalization of chronic total occlusions from the transradial approach; early Canadian experience. Catheter Cardiovasc Interv. 2011;78: Brilakis ES, Grantham JA, Rinfret S, Wyman RM, Burke MN, Karmpaliotis D, Lembo N, Pershad A, Kandzari DE, Buller CE, DeMartini T, Lombardi WL, Thompson CA. A percutaneous treatment algorithm for crossing coronary chronic total occlusions. JACC Cardiovasc Interv. 2012;5: Michael TT, Papayannis AC, Banerjee S, Brilakis ES. Subintimal dissection/reentry strategies in coronary chronic total occlusion interventions. Circ Cardiovasc Interv. 2012;5: Lemeshow S, Hosmer DW Jr. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol. 1982;115: Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143: Valenti R, Vergara R, Migliorini A, Parodi G, Carrabba N, Cerisano G, Dovellini EV, Antoniucci D. Predictors of reocclusion after successful drug-eluting stent-supported percutaneous coronary intervention of chronic total occlusion. J Am Coll Cardiol. 2013;61: Syrseloudis D, Secco GG, Barrero EA, Lindsay AC, Ghione M, Kilickesmez K, Foin N, Martos R, Di Mario C. Increase in J-CTO lesion complexity score explains the disparity between recanalisation success and evolution of chronic total occlusion strategies: insights from a singlecentre 10-year experience. Heart. 2013;99: Galassi AR, Tomasello SD, Reifart N, Werner GS, Sianos G, Bonnier H, Sievert H, Ehladad S, Bufe A, Shofer J, Gershlick A, Hildick-Smith D, Escaned J, Erglis A, Sheiban I, Thuesen L, Serra A, Christiansen E, Buettner A, Costanzo L, Barrano G, Di Mario C. In-hospital outcomes of percutaneous coronary intervention in patients with chronic total occlusion: insights from the ERCTO (European Registry of Chronic Total Occlusion) registry. EuroIntervention. 2011;7: Michael TT, Karmpaliotis D, Brilakis ES, Fuh E, Patel VG, Mogabgab O, Alomar M, Kirkland BL, Lembo N, Kalynych A, Carlson H, Banerjee S, Lombardi W, Kandzari DE. Procedural outcomes of revascularization of chronic total occlusion of native coronary arteries (from a multicenter United States registry). Am J Cardiol. 2013;112: Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, Taggart D. Guidelines on myocardial revascularization. Eur Heart J. 2010;31: