Methods

All consecutive patients with a coronary CTO (100% stenosis with anterograde Thrombolysis In Myocardial Infarction 0 flow for >3 months), catheterized at our institution from January to October 2014, were included. The only exclusion criterion was a history of coronary artery bypass graft (CABG). As this was a retrospective analysis conducted per institutional guidelines for data security and privacy, a waiver of consent was granted by the local institutional review board.

Preexisting co-morbidities and the indication of coronary angiogram were collected. General angiographic data included the number of narrowed vessels and the SYNTAX score (calculated using the online tool available at http://www.syntaxscore.com/ ). The CTO SYNTAX score (CTO-SS) was defined as the ratio between the score attributed to the CTO lesion and the SYNTAX score. If >1 CTO was present, the numerator of the CTO-SS was calculated as the sum of the scores attributed to each CTO. A CTO-SS ≤0.5 was considered “low” and a value >0.5 was considered “high.” The Japanese chronic total occlusion (J-CTO) score was also calculated for each lesion. In addition, the following variables were analyzed: CTO age, interventional collaterals grade (according to the Werner classification ), and distal vessel filling (Rentrop grade ≥2 ). All angiograms were reviewed by an interventional cardiologist who had received extensive training at the local quantitative coronary analysis core laboratory.

Patient management was classified as percutaneous coronary intervention (PCI), CABG, or medical therapy (MT). To analyze the decision-making process, the following variables were recorded: the presence of symptoms (angina or dyspnea), indication of heart surgery (SYNTAX score >22 with/without valve disease), viability in the CTO-related territory on noninvasive testing (as assessed by Tomasello et al ), high co-morbidity or high risk for revascularization (as assessed by the Heart Team), and the suitability of the target distal vessel for revascularization (diameter >2.0 mm and nonnegligible distal bed length).

In case of normality, continuous variables are presented as mean ± SD and the Student t test was used for comparisons. Otherwise, they are presented as median (first to third quartiles), and nonparametric tests were used for comparisons. Categorical variables are presented as frequencies (percentages) and compared using the chi-square test.

Stratified analyses of patient management were performed according to SYNTAX score, J-CTO score, and CTO-SS. In addition, management strategies were analyzed in 5 hypothetical scenarios, as previously described. Scenario 1: presence of symptoms and viability; scenario 2: presence of symptoms but viability testing not performed; scenario 3: absence of symptoms with the presence of viability; scenario 4: absence of symptoms and viability testing not performed; and scenario 5: absence of viability.

Predictors of revascularization (PCI, CABG, or both) were sought. Candidate variables included: age, gender, body mass index (BMI), diabetes, severe angina, left ventricular ejection fraction (LVEF), Q waves concordant with CTO localization, number of CTOs, CTO localization in the left anterior descending (LAD), J-CTO score, SYNTAX score, CTO age, interventional collaterals, distal filling, and viability in the CTO-related artery. The CTO-SS was not included as a candidate predictor because it is a codependent variable with the SYNTAX score. Variables showing a p <0.20 in univariate analysis were used as candidate predictors for stepwise logistic regression analysis (entry and exit criteria set at p <0.10).

Multivariate Cox regression analysis was performed to ascertain whether successful CTO revascularization (either percutaneous or surgical) was associated with better outcomes on follow-up, as compared with unsuccessful revascularization (failed CTO PCI or CABG with no graft to the CTO-related artery) or MT. Due to low number of events, the analyses were adjusted for a reduced number of variables, chosen based on clinical judgment, as follows. Prediction of death: age and SYNTAX score. Prediction of a composite of death, myocardial infarction (MI), any revascularization, ventricular tachycardia/ventricular fibrillation (VT/VF) and readmission for angina: age, gender, diabetes, SYNTAX score, LVEF, chronic kidney disease, and LAD CTO. Prediction of a composite of death, MI, and CTO revascularization: age, SYNTAX score, LVEF. Adjusted Kaplan–Meier curves of event-free survival were plotted and compared with the log-rank test. For all tests, a p <0.05 was considered significant. Statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, North Carolina).

Results

A total of 510 patients with 597 CTOs were included. CTO prevalence was 12% in the overall catheterization laboratory population and 20% in patients with CAD excluding post-CABG subjects ( Figure 1 ). Most patients had 1 CTO (n = 430, 84%); 73 patients had 2 CTOs (14%); and 7 patients had 3 CTOs (1%). Patients were managed as follows: 57% of patients were treated medically, 34% underwent CABG; and 9% underwent CTO PCI. As detailed in Table 1 , PCI patients had worse angina class and were younger and more overweight than CABG and MT subjects. Moreover, these patients presented more often with stable CAD and had a lower prevalence of diabetes, peripheral artery disease, and chronic kidney disease.

Flowchart of the study population.

Angiographic data are presented in Table 2 . The SYNTAX score was lowest in patients treated with PCI (14.8 [11.0 to 18.5]) and highest in CABG subjects (31.5 [25.0 to 38.8], p <0.0001). Not all classic angiographic considerations influenced management patterns. Localization of the CTO, presence and degree of interventional collaterals, and distal vessel filling did not favor a treatment strategy over another. Anatomical complexity of CTO lesions was lower in PCI patients, as shown by the J-CTO score (1.18 ± 1.10), compared with the CABG (1.75 ± 1.11) and MT (1.60 ± 1.02) groups (p = 0.002).

As listed in Table 3 , the vast majority of patients in all groups were symptomatic. Most patients treated with CABG (91%) had a formal indication of surgical revascularization. CABG-treated patients had a higher prevalence of viability in the CTO territory. Only 9% of subjects managed with MT had a CTO vessel not amenable to revascularization.

Table 3

Decision-making process

Variable		Overall (n=510)	PCI (n=48)	CABG (n=172)	Medical therapy (n=290)	p
Presence of symptoms		451 (88%)	43 (90%)	164 (95%)	244 (84%)	0.001
Indication of heart surgery		231 (45%)	4 (8%)	157 (91%)	70 (24%)	<0.0001
Viability testing	Viability	345 (68%)	33 (69%)	134 (78%)	178 (61%)	0.003
	No viability	32 (6%)	2 (4%)	4 (2%)	26 (9%)
	Test not performed	133 (26%)	13 (27%)	34 (20%)	86 (30%)
High comorbidity / high risk		42 (8%)	2 (4%)	18 (10%)	22 (8%)	0.31
Vessel not amenable to revascularization		32 (6%)	0	7 (4%)	25 (9%)	0.03

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