eISSN: 1897-4295
ISSN: 1734-9338
Advances in Interventional Cardiology/Postępy w Kardiologii Interwencyjnej
Current issue Archive Manuscripts accepted About the journal Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
1/2019
vol. 15
 
Share:
Share:
more
 
 
Original paper

Differences in patients and lesion and procedure characteristics depending on the age of the coronary chronic total occlusion

Krzysztof L. Bryniarski, Gerald S. Werner, Kambis Mashayekhi, Jarosław Wójcik, David Hildick-Smith, George Sianos, Alfredo R. Galassi, Roberto Garbo, Carlo Di Mario, Kamil Fijorek, Nicolas Boudou, Nicolaus Reifart, Leszek Bryniarski

Adv Interv Cardiol 2019; 15, 1 (55): 28–41
Online publish date: 2019/01/21
Article file
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Summary

In our study, longer chronic total occlusion (CTO) duration was associated with longer procedure time, greater volume of dye used and lower revascularization success. However, it did not influence the in-hospital adverse event rate. This should be taken into account when planning procedures of CTO older than 12 months. Moreover, in our study longer CTO duration was associated with lower procedural success.

Introduction

Chronic total occlusion (CTO) is present in about 16% to 30% of patients undergoing coronary angiography [13]. Despite the increased experience due to the growth of the number of the performed procedures and the introduction of new techniques and equipment, CTO still remains one of the most demanding procedures in interventional cardiology. Using large registry databases, differences in outcomes and revascularization success in patients with CTO were published during the past years [49]. However, as determining age of the CTO may be very challenging, most of them did not include this factor in the analysis. There are several reports describing how and whether CTO duration may affect lesion and procedural characteristics [1014].

However, none of those studies focused on such a large cohort of patients treated in recent years, and therefore benefiting the most from the latest developments in the field of CTO.

Material and methods

The European Registry of CTOs (ERCTO) is a prospective real-world monitored based registry involving over 100 centers across Europe including patients treated with CTO percutanous coronary intervention (PCI) [6].

For the purpose of our study we included patients admitted to the hospitals between January 2015 and the end of April 2017. The treatment indication for CTO was symptomatic myocardial ischemia and/or evidence of reversible myocardial ischemia by perfusion imaging or stress testing. Registry data from both members and associates of the Euro CTO Club were included. Only patients with certain or likely CTO duration were included in the analysis. Out of 10699 patients in the database recruited during the selected period of time, 5933 patients were excluded due to undetermined age of the occlusion. Out of the remaining 4766 patients we excluded 287 patients with an additional acute coronary syndrome and 435 patients with insufficient further data regarding the occlusion characteristics. In the end, a total of 4044 patients were included in the data analysis (Figure 1). Patients were divided into 3 groups according to age of the CTO: 1) 3–6 months; 2) 7–12 months; 3) over 12 months.

Figure 1

Flow chart. Out of 10699 patients in the database recruited during the selected period of time, 5933 patients were excluded due to undetermined age of the occlusion. Out of the remaining 4766 patients we excluded 287 patients with an additional acute coronary syndrome and 435 patients with insufficient further data regarding the occlusion characteristics. In the end a total of 4044 patients were included in the data analysis

/f/fulltexts/PWKI/34711/PWKI-15-34711-g001_min.jpg

Coronary CTO was defined as angiographic evidence of total occlusions with thrombolysis in myocardial infarction (TIMI) flow grade of 0 and estimated duration of at least 3 months. The length of coronary occlusions was estimated from angiographic projections. Degree of calcification was estimated visually on fluoroscopy. Moderate and severe calcifications were defined as calcium extending for less than half or equal/greater than half of the total CTO segment, respectively. The assessment of collateral connections was made according to the Werner classification (CC) [15]. Occlusion duration in the ERCTO was divided into 3 levels of certainty (certain and angiographically confirmed; likely and clinically confirmed; undetermined), as suggested by the Euro CTO Club consensus document [16]. Procedural success was defined as angiographic success (final residual stenosis < 30% by visual estimation and TIMI flow grade of 3 after CTO recanalization). In-hospital adverse events (AEs) were defined as the composite of non-Q-wave and Q-wave myocardial infarction (MI), coronary perforation requiring intervention, recurrent angina requiring urgent repeat revascularization with PCI or coronary bypass surgery, major bleeding, stent thrombosis, stroke, and death. The complexity of CTO lesion was assessed through the J-CTO (Multicenter CTO Registry in Japan) score and the clinical and lesion-related (CL) score [17, 18].

Statistical analysis

Categorical variables are presented as counts and percentages (%). The median (25th–75th percentiles) is reported for continuous data. Fisher’s exact test or c2 test was used for categorical variables, and the Mann-Whitney U test was used to compare continuous variables. Multivariable logistic regression analyses were performed to determine the independent predictors for lesion and procedural characteristics. Univariate analysis was performed for all variables in the study, then the variables with p < 0.05 were included in the multivariable models for adjusted analysis. Statistical analyses were performed with R 3.4.

Results

A total of 4044 of patients were included in the main analysis. Patients with the longest CTO duration as compared to patients with CTO duration 3–6 months were significantly older (63.0 (56.0–70.0) vs. 66.0 (59.0–73.0) years) and had higher prevalence of peripheral artery disease (8.8% vs. 12.4%) (Table I). The group with the longest CTO duration had higher incidence of myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) as compared to other groups. Lesion and procedural characteristics also differed between patients with different age of the CTO (Tables II, III). Patients with the longest CTO duration as compared to patients with CTO duration 3–6 months had longer occlusions (28.0 (20.0–40.0) vs. 20.0 (15.0–30.0) mm), more calcified lesions (calcification moderate or severe; 51.6% vs. 34.4%), better collateral circulation (30.1% vs. 24.7% for CC2) and more advanced coronary artery disease distal to CTO (48.8% vs. 34.5%). The revascularization success rate was the highest in the patients with CTO duration 3–6 months as compared to the patients with the oldest CTO (92.1% vs. 83.5%), and the retrograde approach was less common in those lesions (24.2% vs. 38.5%). Intravascular ultrasound was used more frequently in the older occlusions (15.7% vs. 9.5%). Incidence of in-hospital AEs increased from 2.0% in the group with the shortest CTO duration to 3.6% in the group with the longest CTO duration (Table III). Time of the procedure and dye volume increased significantly with increased CTO duration, reaching up to 120 min and 250 ml of dye used in the last group (Table III). The J-CTO score as well as the CL score were higher in older lesions (Figure 2).

Table I

Clinical characteristics of patients depending on the chronic total occlusion age

Parameter3–6 months (n = 1415)7–12 months (n = 973)> 12 months (n = 1656)Overall p-value
Age [years]63.0 (56.0–70.0)63.0 (56.0–71.0)66.0 (59.0–73.0)< 0.001
Gender (male), n (%)1197 (84.7)812 (83.5)1440 (87.0)0.030
BMI [kg/m2]27.8 (25.3–31.1)27.8 (25.3–31.1)28.3 (25.6–31.1)0.077
Hypertension, n (%)1097 (77.5)787 (80.9)1369 (82.7)0.002
Diabetes, n (%)426 (31.8)288 (31.6)539 (35.4)0.062
Hypercholesterolemia, n (%)1137 (80.4)762 (78.3)1317 (79.5)0.479
Smokers, n (%)334 (25.0)220 (24.1)299 (19.6)0.001
PAD, n (%)124 (8.8)98 (10.1)206 (12.4)0.004
Previous MI, n (%)557 (40.0)394 (41.1)818 (51.2)< 0.001
Previous CABG, n (%)116 (8.2)96 (9.9)486 (29.4)< 0.001
Previous PCI, n (%)682 (48.2)481 (49.4)913 (55.2)< 0.001
GFR [ml/min/1.73 m2]91.2 (70.4–111.3)91.2 (71.6–112.2)84.0 (66.7–108.2)< 0.001
Left ventricular EF < 35, n (%)78 (5.5)49 (5.1)120 (7.3)0.039
3-vessel disease, n (%)449 (32.2)294 (30.9)749 (46.1)< 0.001

[i] Values are median (25th–75th percentile) or n (%). BMI – body mass index, CABG – coronary artery bypass grafting, EF – ejection fraction, GFR – glomerular filtration rate, MI – myocardial infarction, PAD – peripheral artery disease, PCI – percutaneous coronary intervention.

Table II

Lesion characteristics depending on the chronic total occlusion age

Parameter3–6 months (n = 1415)7–12 months (n = 973)> 12 months (n = 1656)Overall p-value
CTO artery0.001
RCA, n (%)773 (54.7)545 (56.0)998 (60.3)
LM, n (%)6 (0.4)5 (0.5)19 (1.1)
LAD, n (%)393 (27.8)250 (25.7)342 (20.7)
Cx, n (%)235 (16.6)168 (17.3)288 (17.4)
CTO in bypass, n (%)5 (0.4)5 (0.5)8 (0.5)
Ostial CTO, n (%)154 (10.9)102 (10.5)254 (15.4)< 0.001
Vessel diameter [mm]3.0 (2.5–3.0)3.0 (2.7–3.0)3.0 (2.7–3.0)0.006
CTO length [mm]20.0 (15.0–30.0)25.0 (15.0–30.0)28.0 (20.0–40.0)< 0.001
Collateral circulation type 2, n (%)333 (24.7)274 (29.5)474 (30.1)0.002
Proximal tortuosity, n (%)271 (19.4)162 (16.9)332 (20.6)0.073
In CTO bend, n (%)388 (27.5)330 (34.2)614 (37.3)< 0.001
Moderate and severe calcification, n (%)486 (34.4)370 (38.3)851 (51.6)< 0.001
Blunt stump, n (%)610 (43.3)405 (41.7)734 (44.5)0.366
Severe distal disease, n (%)475 (34.5)353 (38.0)783 (48.8)< 0.001

[i] Values are median (25th–75th percentile) or n (%). CTO – chronic total occlusion, Cx – circumflex artery, LAD – left anterior descending artery, LM – left main artery, RCA – right coronary artery.

Table III

Procedural characteristics depending on the chronic total occlusion age

Parameter3–6 months (n = 1415)7–12 months (n = 973)> 12 months (n = 1656)Overall p-value
One or more previous attempts, n (%)470 (33.2%)319 (32.8%)563 (34.0%)0.789
Retrograde approach, n (%)342 (24.2%)237 (24.4%)638 (38.5%)< 0.001
Procedural failure, n (%)112 (7.9%)109 (11.2%)273 (16.5%)< 0.001
AE, n (%)29 (2.0%)24 (2.5%)60 (3.6%)0.024
Procedure time85.0 (57.0–120.0)90.0 (63.0–127.0)120.0 (77.0–162.0)< 0.001
Fluoroscopy time31.5 (19.0–53.0)32.5 (20.0–52.0)45.0 (27.0–70.0)< 0.001
Dye used237.0 (170.0–330.0)250.0 (170.0–350.0)250.0 (190.0–350.0)< 0.001

[i] Values are median (25th–75th percentile) or n (%). AE – adverse events.

Figure 2

Differences in J-CTO score (A) and CL score (B) depending on the chronic total occlusion age. Differences in J-CTO score between patients with different chronic total occlusion (CTO) duration were significant (3968 patients; p < 0.001). J-CTO score of 3 or more increased with increase of the lesion age. In the CL score only patients with a first attempt were included in the analysis (2692 patients). Differences in CL score depending on the occlusion duration were significant (p < 0.001) and prevalence of a CL score of more than 5 points increased with the lesion age

/f/fulltexts/PWKI/34711/PWKI-15-34711-g002_min.jpg

In multivariate analysis (univariate analysis is presented in Table IV) we found that CTO duration was an independent predictor of lesion length, severity of calcification, better developed collateral circulation and procedure failure, but it did not influence the AE rate (Table V). Full multivariate analysis is presented in Table VI.

Table IV

Univariate analysis for lesion characteristics

ParameterModerate/severe calcification (n = 2320)Mild/no calcification (n = 1701)P-value
Age [years]63.0 (55.0–70.0)66.0 (59.0–74.0)< 0.001
Gender (male), n (%)1961 (84.6)1472 (86.3)0.139
BMI [kg/m2]27.8 (25.4–31.1)28.1 (25.5–31.2)0.135
Hypertension, n (%)1808 (77.9)1435 (84.1)< 0.001
Hypercholesterolemia, n (%)1819 (78.4)1385 (81.1)0.037
Diabetes, n (%)640 (29.5)609 (38.4)< 0.001
Smoker, n (%)544 (25.1)305 (19.2)< 0.001
PAD, n (%)187 (8.1)239 (14.0)< 0.001
COPD, n (%)85 (3.7)110 (6.4)< 0.001
Prior stroke, n (%)64 (2.8)45 (2.6)
Previous MI, n (%)1047 (45.9)714 (43.2)0.1
Previous CABG, n (%)269 (11.6)426 (25.0)< 0.001
Previous PCI, n (%)1144 (49.3)922 (54.0)0.004
GFR [ml/min/1.73 m2]91.2 (71.5–113.6)84.2 (65.5–107.2)< 0.001
Left ventricular EF < 35%, n (%)143 (6.2)103 (6.1)0.91
Number of diseased vessels, n (%):< 0.001
 1-vessel disease823 (36.2)392 (23.3)
 2-vessel disease736 (32.4)514 (30.6)
 3-vessel disease715 (31.4)773 (46.0)
CTO artery, n (%):< 0.001
 RCA1248 (53.9)1061 (62.2)
 LAD597 (25.8)383 (22.4)
 Cx451 (19.5)235 (13.8)
 LM3 (0.1)27 (1.6)
 CTO in bypass17 (0.7)1 (0.1)
 CTO in side branch78 (3.4)34 (2.0)0.012
 Ostial CTO227 (9.8)281 (16.5)< 0.001
Occlusion duration, n (%):< 0.001
 3–6 months486 (28.5)925 (39.9)
 7–12 months370 (21.7)596 (25.7)
 Over 12 months851 (49.9)799 (34.4)
ParameterCC2 (n = 2772)CC0/CC1 (n = 1081)P-value
Age [years]64.0 (57.0–72.0)64.0 (57.0–72.0)0.917
Gender (male), n (%)2331 (84.2)951 (88.0)0.003
BMI [kg/m2]28.1 (25.4–31.1)27.8 (25.4–31.1)0.372
Hypertension, n (%)2236 (80.7)864 (79.9)0.636
Hypercholesterolemia, n (%)2206 (79.6)859 (79.5)0.97
Diabetes, n (%)878 (33.7)308 (30.7)0.087
Smoker, n (%)592 (22.7)231 (23.0)0.9
PAD, n (%)282 (10.2)127 (11.7)0.171
COPD, n (%)133 (4.8)57 (5.3)0.597
Prior stroke, n (%)71 (2.6)34 (3.1)0.373
Previous MI, n (%)1214 (44.8)464 (44.1)0.743
Previous CABG, n (%)448 (16.2)214 (19.8)0.008
Previous PCI, n (%)1428 (51.5)550 (50.9)0.742
GFR [ml/min/1.73 m2]89.0 (68.8–110.7)89.1 (69.8–111.3)0.5
Left ventricular EF < 35%, n (%)182 (6.6)48 (4.5)0.018
Number of diseased vessels, n (%):< 0.001
 1-vessel disease790 (28.9)372 (35.4)
 2-vessel disease873 (32.0)323 (30.7)
 3-vessel disease1067 (39.1)357 (33.9)
CTO artery, n (%):< 0.001
 RCA1555 (56.2)681 (63.0)
 LAD666 (24.1)261 (24.1)
 Cx521 (18.8)126 (11.7)
 LM14 (0.5)12 (1.1)
 CTO in bypass12 (0.4)1 (0.1)
 CTO in side branch96 (3.5)10 (0.9)< 0.001
 Ostial CTO330 (11.9)163 (15.2)0.008
Occlusion duration, n (%):0.003
 3–6 months333 (30.8)1013 (36.5)
 7–12 months274 (25.3)656 (23.7)
 Over 12 months474 (43.8)1103 (39.8)
ParameterLesion length < 20 mm (n = 1167)Lesion length > 20 mm (n = 2832)P-value
Age [years]65.0 (58.0–73.0)64.0 (57.0–71.0)0.015
Gender (male), n (%)973 (83.4)2438 (86.1)0.034
BMI [kg/m2]27.8 (25.3–30.8)28.0 (25.5–31.2)0.032
Hypertension, n (%)930 (79.7)2287 (80.8)0.467
Hypercholesterolemia, n (%)944 (80.9)2237 (79.0)0.19
Diabetes, n (%)356 (32.3)885 (33.7)0.45
Smoker, n (%)233 (21.2)614 (23.4)0.155
PAD, n (%)100 (8.6)322 (11.4)0.01
COPD, n (%)51 (4.4)144 (5.1)0.383
Prior stroke, n (%)32 (2.7)78 (2.8)1
Previous MI, n (%)471 (41.2)1282 (46.4)0.003
Previous CABG, n (%)163 (14.0)524 (18.5)0.001
Previous PCI, n (%)551 (47.2)1497 (52.9)0.001
GFR [ml/min/1.73 m2]87.0 (68.5–108.2)89.2 (69.1–111.4)0.159
Left ventricular EF < 35%, n (%)68 (5.9)178 (6.3)0.629
Number of diseased vessels, n (%):0.044
 1-vessel disease372 (32.6)838 (30.1)
 2-vessel disease376 (32.9)867 (31.2)
 3-vessel disease394 (34.5)1078 (38.7)
CTO artery, n (%):< 0.001
 RCA538 (46.2)1747 (61.7)
 LAD349 (30.0)629 (22.2)
 Cx263 (22.6)421 (14.9)
 LM12 (1.0)18 (0.6)
 CTO in bypass2 (0.2)16 (0.6)
 CTO in side branch59 (5.1)51 (1.8)< 0.001
 Ostial CTO110 (9.4)389 (13.8)< 0.001
Occlusion duration, n (%):< 0.001
 3–6 months514 (44.0)890 (31.4)
 7–12 months277 (23.7)687 (24.3)
 Over 12 months376 (32.2)1255 (44.3)
Age [years]66.0 (60.0–73.0)64.0 (57.0–72.0)< 0.001
Gender (male), n (%)423 (85.8)3026 (85.3)0.804
BMI [kg/m2]28.4 (26.0–31.6)27.9 (25.4–31.1)0.014
Hypertension, n (%)410 (83.0)2843 (80.1)0.142
Hypercholesterolemia, n (%)386 (78.1)2830 (79.7)0.45
Diabetes, n (%)181 (39.4)1072 (32.4)0.003
Smoker, n (%)92 (20.0)761 (23.0)0.179
PAD, n (%)80 (16.2)348 (9.8)< 0.001
COPD, n (%)40 (8.1)156 (4.4)0.001
Prior stroke, n (%)22 (4.5)88 (2.5)0.017
Previous MI, n (%)234 (49.0)1535 (44.3)0.059
Previous CABG, n (%)115 (23.3)583 (16.4)< 0.001
Previous PCI, n (%)299 (60.5)1777 (50.1)< 0.001
GFR [ml/min/1.73 m2]84.7 (66.4–106.9)89.1 (69.4–111.0)0.016
Left ventricular EF < 35%, n (%)34 (7.0)213 (6.0)0.488
Number of diseased vessels, n (%):0.213
 1-vessel disease136 (28.2)1086 (31.2)
 2-vessel disease148 (30.7)1106 (31.7)
 3-vessel disease198 (41.1)1294 (37.1)
CTO artery, n (%):0.02
 RCA316 (64.0)2000 (56.4)
 LAD102 (20.6)883 (24.9)
 Cx74 (15.0)617 (17.4)
 LM1 (0.2)29 (0.8)
 CTO in bypass1 (0.2)17 (0.5)
 CTO in side branch10 (2.0)102 (2.9)0.35
 Ostial CTO97 (19.7)413 (11.7)< 0.001
 In stent CTO31 (6.3)367 (10.3)0.006
Bifurcation, n (%)130 (26.3)992 (27.9)0.482
Vessel diameter [mm]3.0 (2.8–3.0)3.0 (2.5–3.0)0.839
CTO length [mm]30.0 (20.0–40.0)25.0 (15.0–35.0)< 0.001
Collateral circulation type 2, n (%)118 (25.1)963 (28.5)0.135
Proximal tortuosity, n (%)134 (27.7)631 (18.1)< 0.001
In CTO bend, n (%)254 (52.4)1078 (30.5)< 0.001
Moderate and severe calcification, n (%)307 (62.8)1400 (39.6)< 0.001
Blunt stump, n (%)243 (49.4)1506 (42.6)0.005
Side branch 3 mm proximal to CTO, n (%)133 (26.9)943 (26.6)0.908
Visible distal opacification, n (%)143 (29.2)1652 (46.7)< 0.001
Severe distal disease, n (%)251 (53.0)1360 (39.6)< 0.001
One or more previous attempts, n (%)185 (37.4)1167 (32.9)0.049
Retrograde approach, n (%)207 (41.9)1010 (28.5)< 0.001
AE, n (%)24 (4.9)89 (2.5)0.005
Occlusion duration, n (%):< 0.001
 3–6 months112 (22.7)1303 (36.7)
 7–12 months109 (22.1)864 (24.3)
 Over 12 months273 (55.3)1383 (39.0)
ParameterNon-AE (n = 3931)AE (n = 113)P-value
Age [years]64.0 (57.0–72.0)66.0 (59.0–73.0)0.056
Gender (male), n (%)3363 (85.6)86 (76.1)0.007
BMI [kg/m2]28.0 (25.5–31.1)27.7 (24.8–31.1)0.275
Hypertension, n (%)3154 (80.2)99 (87.6)0.067
Hypercholesterolemia, n (%)3119 (79.3)97 (85.8)0.117
Diabetes, n (%)1220 (33.3)33 (31.7)0.825
Smoker, n (%)834 (22.7)19 (18.3)0.339
PAD, n (%)407 (10.4)21 (18.6)0.008
COPD, n (%)186 (4.7)10 (8.8)0.074
Prior stroke, n (%)103 (2.6)7 (6.2)0.033
Previous MI, n (%)1709 (44.6)60 (53.6)0.073
Previous CABG, n (%)674 (17.2)24 (21.2)0.314
Previous PCI, n (%)2017 (51.3)59 (52.2)0.927
GFR [ml/min/1.73 m2]89.0 (69.0–110.8)81.2 (67.3–101.7)0.013
Left ventricular EF < 35%, n (%)235 (6.0)12 (10.6)0.07
Number of diseased vessels, n (%):0.683
 1-vessel disease1192 (30.9)30 (27.0)
 2-vessel disease1217 (31.6)37 (33.3)
 3-vessel disease1448 (37.5)44 (39.6)
CTO artery, n (%):0.707
 RCA2254 (57.4)62 (54.9)
 LAD956 (24.3)29 (25.7)
 Cx670 (17.1)21 (18.6)
 LM30 (0.8)0 (0.0)
 CTO in bypass17 (0.4)1 (0.9)
 CTO in side branch108 (2.8)4 (3.5)0.555
 Ostial CTO, n (%)494 (12.6)16 (14.2)0.728
 In stent CTO, n (%)391 (9.9)7 (6.2)0.246
Bifurcation, n (%)1085 (27.6)37 (32.7)0.273
Vessel diameter [mm]3.0 (2.5–3.0)3.0 (2.5–3.0)0.805
CTO length [mm]25.0 (15.0–35.0)30.0 (18.0–40.0)0.136
Collateral circulation type 2, n (%)1043 (27.9)38 (33.9)0.195
Proximal tortuosity, n (%)750 (19.5)15 (13.4)0.138
In CTO bend, n (%)1285 (32.9)47 (41.6)0.067
Moderate and severe calcification, n (%)1658 (42.4)49 (43.4)0.908
Blunt stump, n (%)1702 (43.5)47 (41.6)0.765
Side branch 3 mm proximal to CTO, n (%)1041 (26.5)35 (31.0)0.338
Visible distal opacification, n (%)1743 (44.6)52 (46.0)0.834
Severe distal disease, n (%)1567 (41.3)44 (38.9)0.69
One or more previous attempts, n (%)1315 (33.5)37 (32.7)0.955
Retrograde approach, n (%)1165 (29.6)52 (46.0)< 0.001
Procedural failure, n (%)470 (12.0)24 (21.2)0.005
Occlusion duration, n (%):0.024
 3–6 months1386 (35.3)29 (25.7)
 7–12 months949 (24.1)24 (21.2)
 Over 12 months1596 (40.6)60 (53.1)

[i] Values are median (25th – 75th percentile) or n (%). AE – adverse events, BMI – body mass index, CABG – coronary artery bypass grafting, COPD – chronic obstructive pulmonary disease, CTO – chronic total occlusion, Cx – circumflex artery, EF – ejection fraction, GFR – glomerular filtration rate, LAD – left anterior descending artery, LM – left main artery, MI – myocardial infarction, PAD – peripheral artery disease, PCI – percutaneous coronary intervention, RCA – right coronary artery. For calcification, lesion length and collateral circulation only clinical predictors were included in the analysis. For procedural success and AE clinical, lesion characteristics and retrograde approach were included in the analysis.

Table V

Predictors for lesion characteristics and adverse events – multivariate analysis

VariableOR95% CI lower bound95% CI upper boundP-value
Calcification (moderate or severe):
 Occlusion duration 7–12 months1.140.951.380.165
 Occlusion duration > 12 months1.521.281.8< 0.001
Collateral circulation type 2:
 Occlusion duration 7–12 months1.261.031.530.021
 Occlusion duration > 12 months1.21.011.430.041
Lesion length 20 mm:
 Occlusion duration 7–12 months1.431.191.72< 0.001
 Occlusion duration > 12 months1.771.492.1< 0.001
Procedural success:
 Occlusion duration 7–12 months0.780.571.060.116
 Occlusion duration > 12 months0.60.460.79< 0.001
AE:
 Occlusion duration 7–12 months1.170.672.030.578
 Occlusion duration > 12 months1.560.982.470.06

[i] Only results for occlusion duration (as compared to occlusion duration 3–6 months) are presented in the table. Full multivariate analysis is presented in Table VI. AE – adverse events, CI – confidence interval, CTO – chronic total occlusion, OR – odds ratio. Number of patients included in the analysis (n): calcification (moderate or severe), n = 3589; collateral circulation type 2, n = 3739; Lesion length 20 mm, n = 3815; AE, n = 4037.

Table VI

Full multivariate analysis

ParameterOR95% CI lower bound95% CI upper boundP-value
Calcification (moderate or severe):
 Age1.031.021.04< 0.001
 Gender (male)1.311.061.610.011
 BMI1.0211.030.038
 Occlusion duration 7–12 months11.140.951.380.165
 Occlusion duration over 12 months11.521.281.8< 0.001
 Hypertension1.130.941.370.201
 Hypercholesterolemia1.211.011.450.038
 Diabetes1.211.031.410.017
 Smoker0.860.721.030.107
 PAD1.41.111.760.005
 COPD1.641.192.270.003
 Previous CABG1.581.281.96< 0.001
 Previous PCI1.140.981.310.084
 CKD class 42.451.44.310.002
 2-vessel CAD disease1.461.211.75< 0.001
 3- vessel CAD disease1.821.512.2< 0.001
 CTO in bypass20.0200.16< 0.001
 CTO in LAD20.850.721.010.068
 CTO in Cx20.510.410.63< 0.001
 CTO in LM25.311.2123.170.027
 CTO in side branch0.410.260.66< 0.001
 Ostial CTO2.071.662.6< 0.001
Collateral circulation 2:
 Age111.010.472
 Gender (male)1.471.181.830.001
 BMI0.990.981.010.394
 Occlusion duration 7–12 months11.261.031.530.021
 Occlusion duration over 12 months11.21.011.430.041
 Previous CABG1.461.171.820.001
 Left ventricular EF < 35%0.670.480.940.022
 2-vessel CAD disease0.790.660.940.01
 3-vessel CAD disease0.660.540.8< 0.001
 CTO in bypass20.140.021.080.059
 CTO in LAD20.880.741.050.154
CTO in Cx20.570.460.72< 0.001
 CTO in LM21.450.653.230.362
 CTO in side branch0.310.160.60.001
 Ostial CTO1.491.21.85< 0.001
Lesion length > 20 mm:
 Age0.990.9810.019
 Gender (male)1.190.971.450.087
 BMI1.0211.030.05
 Occlusion duration 7–12 months11.431.191.72< 0.001
 Occlusion duration over 12 months11.771.492.1< 0.001
 PAD1.270.991.640.059
 Previous MI1.120.961.30.146
 Previous CABG1.170.931.480.183
 Previous PCI1.191.031.380.022
 2-vessel CAD disease1.030.861.230.749
 3-vessel CAD disease1.170.961.420.112
 CTO in bypass21.710.387.790.488
 CTO in LAD20.60.510.71< 0.001
 CTO in Cx20.520.430.64< 0.001
 CTO in LM20.270.120.610.002
 CTO in side branch0.320.210.48< 0.001
 Ostial CTO1.851.442.37< 0.001
Procedural success:
 Age0.990.9710.015
 Gender (male)10.731.370.997
 BMI0.980.961.010.132
 Occlusion duration 7–12 months10.780.571.060.116
 Occlusion duration over 12 months10.60.460.79< 0.001
 Diabetes0.890.711.120.314
 PAD0.70.510.950.024
 COPD0.610.40.930.022
 Prior stroke0.650.371.120.122
 Previous CABG1.010.761.340.956
 Previous PCI0.610.490.77< 0.001
 CTO in bypass22.990.3724.240.305
 CTO in LAD20.990.751.30.917
 CTO in Cx21.270.921.760.148
 CTO in LM26.480.8350.510.075
 Ostial CTO0.580.430.78< 0.001
 In stent CTO1.91.232.930.004
 Lesion length > 20 mm0.610.460.830.001
 Proximal tortuosity0.850.661.110.239
 In CTO bend0.570.460.71< 0.001
 Moderate/severe calcification0.550.430.7< 0.001
 Blunt stump0.790.630.980.034
 Visible distal opacification1.771.392.24< 0.001
 Severe distal disease0.990.791.260.965
 One or more previous attempts0.870.691.090.231
AE:
 Age1.010.991.030.313
 Gender (male)0.520.330.810.004
 BMI0.980.941.030.44
 Occlusion duration 7–12 months11.170.672.030.578
 Occlusion duration over 12 months11.560.982.470.06
 PAD1.671.022.760.043
 Prior stroke2.090.934.730.075
 Retrograde approach1.931.312.830.001

[i] AE – adverse events, BMI – body mass index, CABG – coronary artery bypass grafting, CAD – coronary artery disease, CI – confidence interval, CKD – chronic kidney disease, COPD – chronic obstructive pulmonary disease, CTO – chronic total occlusion, Cx – circumflex artery, EF – ejection fraction, LAD – left anterior descending artery, LM – left main artery, OR – odds ratio, PAD – peripheral artery disease, PCI – percutaneous coronary intervention. 1As compared to occlusion duration 3–6 months; 2as compared to right coronary artery. For calcification, lesion length and collateral circulation only clinical predictors were included in the analysis. For procedural success and AE clinical, lesion characteristics and retrograde approach were included in the analysis. Number of patients included in the analysis (n): calcification (moderate or severe), n = 3589; collateral circulation type 2, n = 3739; lesion length 20 mm, n = 3815; procedural success, n = 3513; AE, n = 4037.

Differences between patients with undetermined age of the occlusion and known occlusion duration are presented in the Supplement (Table VII). As expected, patients with determined age of occlusion had previous MI and CABG more frequently (37.5% vs. 44.8% and 8.1% vs. 17.3% respectively). The procedural failure rate was similar in both groups (11.9% vs. 12.2%). Interestingly, incidence of AEs was higher in the group with undetermined age of the occlusion (3.7% vs. 2.8%).

Table VII

Comparison between patients with undetermined age of the occlusion and known occlusion duration

ParameterUndetermined age of the occlusion (n = 5033)Known occlusion duration (n = 4044)P-value
Age [years]64.0 (57.0–72.0)64.0 (57.0–72.0)0.862
Gender (male), n (%)4246 (84.4)3449 (85.3)0.239
BMI [kg/m2]27.7 (25.1–30.7)28.0 (25.4–31.1)< 0.001
Hypertension, n (%)3824 (76.0)3253 (80.4)< 0.001
Hypercholesterolemia, n (%)3548 (70.5)3216 (79.5)< 0.001
Diabetes, n (%)1546 (32.9)1253 (33.2)0.78
Smoker, n (%)1367 (29.1)853 (22.6)< 0.001
PAD, n (%)594 (11.8)428 (10.6)0.073
COPD, n (%)262 (5.2)196 (4.8)0.466
Prior stroke, n (%)147 (2.9)110 (2.7)0.611
Previous MI, n (%)1807 (37.5)1769 (44.8)< 0.001
Previous CABG, n (%)406 (8.1)698 (17.3)< 0.001
Previous PCI, n (%)2492 (49.5)2076 (51.3)0.086
GFR [ml/min/1.73 m2]86.9 (67.0–109.4)88.6 (68.9–110.7)0.006
Left ventricular EF < 35%, n (%)412 (8.2)247 (6.1)< 0.001
Number of diseased vessels, n (%):< 0.001
 1-vessel disease1677 (34.4)1222 (30.8)
 2-vessel disease1654 (33.9)1254 (31.6)
 3-vessel disease1549 (31.7)1492 (37.6)
CTO artery, n (%):< 0.001
 RCA2746 (54.7)2316 (57.3)
 LAD1338 (26.6)985 (24.4)
 Cx914 (18.2)691 (17.1)
 LM13 (0.3)30 (0.7)
 CTO in bypass12 (0.2)18 (0.4)
 CTO in side branch110 (2.2)112 (2.8)0.086
 Ostial CTO463 (9.2)510 (12.6)< 0.001
 In-stent CTO369 (7.3)398 (9.8)< 0.001
 Bifurcation1275 (25.3)1122 (27.7)0.01
Vessel diameter [mm]3.0 (2.5–3.0)3.0 (2.5–3.0)0.136
CTO length [mm]25.0 (15.0–35.0)25.0 (15.0–35.0)0.225
Collateral circulation type 2, n (%)1443 (31.5)1081 (28.1)0.001
Proximal tortuosity, n (%)941 (19.0)765 (19.3)0.714
In CTO bend, n (%)1550 (31.0)1332 (33.2)0.034
Moderate and severe calcification, n (%)2182 (43.5)1707 (42.4)0.294
Blunt stump, n (%)2043 (40.7)1749 (43.4)0.01
Visible distal opacification, n (%)2043 (41.0)1795 (44.6)0.001
Severe distal disease, n (%)1721 (38.5)1611 (41.2)0.013
One or more previous attempts, n (%)1115 (22.2)1352 (33.4)< 0.001
Retrograde approach, n (%)1411 (28.0)1217 (30.1)0.033
Procedural failure, n (%)597 (11.9)494 (12.2)0.629
AE, n (%)185 (3.7)113 (2.8)0.019
Radial access, n (%)2324 (46.2)1290 (31.9)< 0.001
Rotablation, n (%)122 (12.4)100 (2.5)0.881
IVUS, n (%)653 (13.0)503 (12.4)0.446
Procedure time90.0 (60.0–129.0)100.0 (63.0–144.0)< 0.001
Fluoroscopy time33.0 (19.0–55.0)37.0 (22.0–60.8)< 0.001
Dye used236.0 (170.0–320.0)250.0 (180.0–350.0)< 0.001

[i] Values are median (25th–75th percentile) or n (%). AE – adverse events, BMI – body mass index, CABG – coronary artery bypass grafting, COPD – chronic obstructive pulmonary disease, CTO – chronic total occlusion, Cx – circumflex artery, EF – ejection fraction, GFR – glomerular filtration rate, LAD – left anterior descending artery, LM – left main artery, MI – myocardial infarction, PAD – peripheral artery disease, PCI – percutaneous coronary intervention, RCA – right coronary artery. Out of 5933 patients with undetermined age of the occlusion, 900 were excluded due to insufficient data regarding the occlusion characteristics. In the end a total of 4044 patients with known occlusion duration and 5033 patients with undetermined age of the occlusion were included in the data analysis.

Discussion

Our study, performed on a large cohort of patients, demonstrated that: 1) longer duration of CTO is associated with longer procedure and fluoroscopy time, and greater amount of dye used; 2) longer duration of CTO is a predictor of greater calcification, longer lesions and more developed collateral circulation; 3) age of the CTO influences the procedure success, but not in-hospital AEs.

Procedure duration

As observed in previous studies, patients with longer CTO duration had longer procedure and fluoroscopy time, as well as a greater amount of dye used [10]. These results should be taken into account when planning a procedure with known age of the CTO.

Calcification

In our study occlusion duration of over 12 months was an independent predictor of calcification. In more advanced coronary artery disease (CAD), elevated lipid content and inflammatory mediators induce osteogenic differentiation of vascular smooth muscle cells in the intima – usually calcific deposits are found more frequently and in greater amounts among more advanced lesions and in elderly individuals [19]. These observations were confirmed in the CTO histopathology study where older lesion age was associated with a greater fibrocalcific component [20]. Comparable to our results, Danek et al. recently observed a difference of 16% in moderate/severe calcification between patients with a CTO duration shorter than 5 and longer than 36.3 months [10]. Moreover, as previously reported, CABG in medical history was also associated with higher prevalence of calcification in CTO lesions [21]. Importantly, calcification is regarded as one of the predictors of failure when performing PCI of CTO – both the CL score proposed by Alessandrino et al. and the J-CTO score include calcification in their scoring systems [17, 18].

Collateral circulation

We observed that occlusion duration longer than 6 months was a predictor of development of collaterals in CC grade 2 proposed by Werner et al. [15]. Time of recruitment of collaterals in CTO is still debatable, ranging from several weeks to months [22]. Collateral flow plays several major roles in CTO. First, well-developed collaterals have the capacity to prevent myocardial necrosis and may preserve myocardial viability [22]. Second, collaterals are used during the retrograde approach and thus poorly developed collaterals were found to be an independent predictor of technical failure in CTO PCI [5, 23].

Lesion length

In contrast to the study of Danek et al., we found that CTO length increased with age of the CTO [10]. In our study, even occlusion duration longer than 6 months was an independent predictor of CTO length over 20 mm. One could speculate that with the novel techniques including the hybrid approach and retrograde revascularization lesion length may be less important in assessing complexity of the CTO procedures as shown in the PROGRESS CTO score and ORA score [5, 23]. In contrast, Ellis et al. showed in their recent study assessing predictors of a successful hybrid approach that procedure failure is correlated with occlusion length over 10 mm [7]. Besides that, longer lesions may still influence the duration of the procedure [17].

Procedural success

Currently several different angiographic scoring systems assessing predictors of failure and success in CTO PCI are available, but none of them has ever included the duration of CTO in their analysis [2426]. On the other hand, CTO duration as predictor of revascularization failure has been described in computed tomography studies [13, 14]. Given the results of those studies and our current study, it is plausible to say that duration of CTO may have an influence on procedural success and PCI of CTO should not be postponed, although this observation merits further research. Nevertheless, it should be underlined that in our study the exact age of CTO lesions could only be determined in less than 50% of the cases; thus implementing CTO duration in future scoring systems may be challenging. Lastly, some of the studies did not find a correlation between CTO duration and procedural success; however, the number of patients included in the analysis was also significantly lower [27].

Adverse events

A weighted meta-analysis by Patel et al. with 18061 patients included from 65 studies revealed low rates of AEs in patients undergoing CTO PCI [2]. In our study rates of AEs were comparable, with 0.4% deaths and 0.7% MI during the hospitalization period. A recent study showed that complications during PCI of CTO were more frequent in females [28]. In concordance with that observation, female gender was one of two AE predictors in our study. Not surprisingly, the retrograde approach was the other predictor of AEs as this approach is considered as more complex when compared to the antegrade approach [6, 29]. However, it should be noted that the retrograde approach is often used in very advanced lesions where the antegrade approach is not feasible or ended with failure. Importantly, although patients with the longest CTO duration had higher incidence of AEs as compared to the patients with the shortest CTO duration, the age of the CTO was not an independent predictor of AEs. Barlis et al. in their study compared AEs in patients with undetermined and known occlusion duration [30]. In long-term follow-up they found that undetermined occlusion duration was a predictor of AEs. In contrast to our study they did not find any differences in in-hospital outcomes between groups with known and unknown occlusion duration. However, their study was limited by the sample size.

Limitations

First, our study is limited by its observational design. Second, angiography-dependent and clinical outcomes were not independently adjudicated. Third, data regarding patients and lesion and procedural characteristics were missing in some cases. Moreover, only in half of the patients could CTO age be assessed. Out of 10 699 patients, 4044 (37.8%) were included in the final analysis, which could have involved selection bias. Further, patients excluded from the study differed from those included in important lesion characteristics such as lesion location, number of previous attempts and severity of coronary artery disease. Lastly, the exact age of the CTO is often unclear. Hence, it is often very challenging to determine the exact age of the CTO.

Conclusions

Longer CTO duration is associated with greater prevalence of calcification, longer lesions, and better developed collateral circulation. Most importantly, in our study longer CTO duration was associated with lower revascularization success by PCI. However, it did not affect the rate of in-hospital AEs. Our results should be taken into account when planning procedures of CTO older than 12 months.

Conflict of interest

The authors declare no conflict of interest.

References

1 

Råmunddal T, Hoebers L, Henriques JPS, et al. , authors. Chronic total occlusions in sweden – a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). PLoS One. 2014. 9:p. e103850

2 

Patel VG, Brayton KM, Tamayo A, et al. , authors. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: a weighted meta-analysis of 18,061 patients from 65 studies. JACC Cardiovasc Interv. 2013. 6:p. 128–36

3 

Fefer P, Knudtson ML, Cheema AN, et al. , authors. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012. 59:p. 991–7

4 

Wolff R, Fefer P, Knudtson ML, et al. , authors. Gender differences in the prevalence and treatment of coronary chronic total occlusions. Catheter Cardiovasc Interv. 2016. 87:p. 1063–70

5 

Galassi AR, Boukhris M, Azzarelli S, et al. , authors. Percutaneous coronary revascularization for chronic total occlusions: a novel predictive score of technical failure using advanced technologies. JACC Cardiovasc Interv. 2016. 9:p. 911–22

6 

Galassi AR, Sianos G, Werner GS, et al. , authors. Retrograde recanalization of chronic total occlusions in Europe: procedural, in-hospital, and long-term outcomes from the multicenter ERCTO registry. J Am Coll Cardiol. 2015. 65:p. 2388–400

7 

Ellis SG, Burke MN, Murad MB, et al. , authors. Predictors of successful hybrid-approach chronic total coronary artery occlusion stenting: an improved model with novel correlates. JACC Cardiovasc Interv. 2017. 10:p. 1089–98

8 

Råmunddal T, Hoebers LP, Henriques JPS, et al. , authors. Prognostic impact of chronic total occlusions: a report from SCAAR (Swedish Coronary Angiography and Angioplasty Registry). JACC Cardiovasc Interv. 2016. 9:p. 1535–44

9 

Wyman RM , author. Do we need another predictive scoring tool for chronic total occlusion percutaneous coronary intervention? JACC Cardiovasc Interv. 2015. 8:p. 1549–51

10 

Danek BA, Karatasakis A, Karmpaliotis D, et al. , authors. Effect of lesion age on outcomes of chronic total occlusion percutaneous coronary intervention: insights from a contemporary US multicenter registry. Canad J Cardiol. 2016. 32:p. 1433–9

11 

Tomasello SD, Costanzo L, Campisano MB, et al. , authors. Does occlusion duration influence procedural and clinical outcome of patients who underwent percutaneous coronary intervention for chronic total occlusion? J Interv Cardiol. 2011. 24:p. 223–31

12 

Choi JH, Kim EK, Kim SM, et al. , authors. Noninvasive discrimination of coronary chronic total occlusion and subtotal occlusion by coronary computed tomography angiography. JACC Cardiovasc Interv. 2015. 8:p. 1143–53

13 

Cho JR, Kim YJ, Ahn CM, et al. , authors. Quantification of regional calcium burden in chronic total occlusion by 64-slice multi-detector computed tomography and procedural outcomes of percutaneous coronary intervention. Int J Cardiol. 2010. 145:p. 9–14

14 

Opolski MP, Achenbach S, Schuhbäck A, et al. , authors. Coronary computed tomographic prediction rule for time-efficient guidewire crossing through chronic total occlusion: insights from the CT-RECTOR multicenter registry (Computed Tomography Registry of Chronic Total Occlusion Revascularization). JACC Cardiovasc Interv. 2015. 8:p. 257–67

15 

Werner GS, Ferrari M, Heinke S, et al. , authors. Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions. Circulation. 2003. 107:p. 1972–7

16 

Sianos G, Werner GS, Galassi AR, et al. , authors. Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention. 2012. 8:p. 139–45

17 

Morino Y, Abe M, Morimoto T, et al. , authors. 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:p. 213–21

18 

Alessandrino G, Chevalier B, Lefèvre T, et al. , authors. A Clinical and Angiographic scoring system to predict the probability of successful first-attempt percutaneous coronary intervention in patients with total chronic coronary occlusion. JACC Cardiovasc Interv. 2015. 8:p. 1540–8

19 

Doherty TM, Detrano RC , authors. Coronary arterial calcification as an active process: a new perspective on an old problem. Calcif Tissue Int. 1994. 54:p. 224–30

20 

Srivatsa SS, Edwards WD, Boos CM, et al. , authors. Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition. J Am Coll Cardiol. 1997. 29:p. 955–63

21 

Sakakura K, Nakano M, Otsuka F, et al. , authors. Comparison of pathology of chronic total occlusion with and without coronary artery bypass graft. Eur Heart J. 2014. 35:p. 1683–93

22 

Werner GS , author. The role of coronary collaterals in chronic total occlusions. Curr Cardiol Rev. 2014. 10:p. 57–64

23 

Christopoulos G, Kandzari DE, Yeh RW, et al. , authors. Development and validation of a novel scoring system for predicting technical success of chronic total occlusion percutaneous coronary interventions: the PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) score. JACC Cardiovasc Interv. 2016. 9:p. 1–9

24 

Karatasakis A, Danek BA, Brilakis ES , authors. Scoring systems for chronic total occlusion percutaneous coronary intervention: if you fail to prepare you are preparing to fail. J Thorac Dis. 2016. 8:p. E1096–9

25 

Karatasakis A, Danek BA, Karmpaliotis D, et al. , authors. Comparison of various scores for predicting success of chronic total occlusion percutaneous coronary intervention. Int J Cardiol. 2016. 224:p. 50–6

26 

Baykan AO, Gür M, Acele A, et al. , authors. Predictors of successful percutaneous coronary intervention in chronic total coronary occlusions. Adv Interv Cardiol. 2016. 12:p. 17–24

27 

de Castro-Filho A, Lamas ES, Meneguz-Moreno RA, et al. , authors. Impact of the occlusion duration on the performance of J-CTO score in predicting failure of percutaneous coronary intervention for chronic total occlusion. J Invasive Cardiol. 2017. 29:p. 195–201

28 

Sharma V, Wilson W, Smith W, et al. , authors. Comparison of characteristics and complications in men versus women undergoing chronic total occlusion percutaneous intervention. Am J Cardiol. 2017. 119:p. 535–41

29 

Dębski M, Dębski A, Tyczyński P, et al. , authors. Retrograde recanalization of chronic total occlusion. A novel maneuver of the old technique. Adv Interv Cardiol. 2017. 13:p. 82–3

30 

Barlis P, Kaplan S, Dimopoulos K, et al. , authors. An indeterminate occlusion duration predicts procedural failure in the recanalization of coronary chronic total occlusions. Catheter Cardiovasc Interv. 2008. 71:p. 621–8

Copyright: © 2019 Termedia Sp. z o. o. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
 
Quick links
© 2019 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe