Catheterization and Cardiovascular Interventions 84:E30–E37 (2014)

CORONARY ARTERY DISEASE Original Studies The Predictors of Successful Percutaneous Coronary Intervention in Ostial Left Anterior Descending Artery Chronic Total Occlusion Hsiu-Yu Fang,1 MD, Shang-Yeh Lu,1 MD, Wei-Chieh Lee,1 MD, Yu-Sheng Lin,2 MD, Cheng-I Cheng,1 MD, Chien-Jen Chen,1 MD, Cheng-Hsu Yang,1 MD, Hon-Kan Yip,1 MD, Chi-Ling Hang,1 MD, Chih-Yuan Fang,1 MD, and Chiung-Jen Wu,1* MD Background: Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the left anterior descending artery (LAD) is one of the most difficult positions for CTO revascularization. Until now, limited data has been made available for the prediction of successful ostial LAD CTO PCI. Objective: The aim of the study was to compare the differences between ostial LAD and all other CTOs and to identify the predictors of successful ostial LAD CTO PCI. Methods: This retrospective analysis included consecutive patients referred for CTO PCI between January 2001 and September 2013. Ostial LAD CTO was defined as CTO at the position whose distance between lesion and left main bifurcation was less than 1 mm. Baseline demographics, lesion characteristics, interventional procedure details, and devices were compared between the ostial LAD group and the all other CTOs group. The predictors of successful ostial LAD CTO PCI were also evaluated. Results: 621 patients who underwent CTO PCI were enrolled retrospectively to this study. A total of 70 patients of ostial LAD CTO were compared with 551 patients of all other CTOs group in this study. Ostial LAD CTO was found to have more bridging and better collaterals than all other CTOs. Procedure time, fluoroscopic time, contrast volumes, the use of contralateral injection, and the use of the retrograde approach were significantly greater in the ostial LAD CTO group. The ostial LAD CTO group also had significantly higher J-CTO scores (2.7 6 0.8 vs. 2.2 6 1.1, P 5 0.011) and higher Syntax Scores (28.3 6 6.5 vs. 20.9 6 9.7, P < 0.001). A slightly lower final success rate, but statistically non-significant, was observed in the ostial LAD CTO group (80.0% vs. 81.9%, P 5 0.706). Univariate and multivariate logistic regression revealed that without antegrade failure and with retrograde success were predictors of the success of ostial LAD CTO PCI. Syntax Score was also capable of predicting the ostial LAD CTO PCI outcome. J-CTO score was not found to be associated with final success for ostial LAD CTO patients. Conclusions: Ostial LAD CTO resulted in higher lesion complexity in J-CTO scores and Syntax Scores. Ostial LAD CTO PCI had a

1

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Chang Gung Institute of Technology, Chiayi, Taiwan

*Correspondence to: Chiung-Jen Wu, MD, No. 123, Ta-Pei Rd, Niao Sung District, Kaohsiung City, 83301, Taiwan. E-mail: [email protected]

Conflict of interest: Nothing to report.

DOI: 10.1002/ccd.25514 Published online 16 April 2014 in Wiley Online Library (wileyonlinelibrary.com)

Hsiu-Yu Fang and Shang-Yeh Lu contributed equally to this work. C 2014 Wiley Periodicals, Inc. V

Received 13 December 2013; Revision accepted 6 April 2014

The Predictor of Successful PCI to Ostium LAD CTO

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slightly lower final success rate than that of all other CTOs PCI with longer procedure duration, fluoroscopic time and larger contrast volume. Without antegrade failure, with retrograde success, and lower Syntax Score were found to predict the success of ostial LAD CTO PCI. VC 2014 Wiley Periodicals, Inc. Key words: chronic total occlusion; ostium; left anterior descending artery; percutaneous coronary intervention

INTRODUCTION

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has become one of the most challenging procedures for interventional cardiologists. The successful recanalization of CTO in patients with viable myocardium decreases the need for bypass surgery, reduces angina symptoms, and improves longterm survival [1–4]. PCI devices and the techniques for CTO have improved in the current era [5], and multiple pilot studies have demonstrated excellent outcomes, especially with the combined use of drug-eluting stents [4,6–8]. The combined use of the antegrade approach and the retrograde approach has markedly increased the overall success rate without increasing the rate of major complications [9–14]. The appropriate use of newly developed techniques and devices raises the success rate and thereby brings an increasing number of CTO into a treatable category [15]. The J-CTO registry has reported the use of J-CTO scores to predict the successful guidewire crossing in CTO within 30 min [16]. The parameters including stump morphology, lesion length >20 mm, calcifica tion, segment bending >45 and re-try lesions define CTO difficulty before PCI [16]. Yet, till now, there has not been any other useful parameter to estimate the CTO difficulty before procedure. Syntax score was first developed as a grading tool for the complexity of coronary artery disease [17], and later used as a risk strategy system guiding interventionists to perform PCI or coronary artery bypass graft (CABG) [18,19]. However, no clinical study has used Syntax Score as a predictor of successful CTO PCI especially in ostial left anterior descending artery (LAD) CTO. The ostial LAD CTO is such a specific location that interventional cardiologists tend to avoid it if possible due to the differences of plaque accumulation and oscillatory shearing forces position at the left main bifurcation [20–22]. Although there was no evidence of specific lower success rate at ostial LAD CTO, there were several reasons to explain the inherent difficulties: the existence of a side branch (left circumflex artery [LCX]), the existence of no stump, the difficult prediction of artery direction, as well as the bifurcation treatment strategies. Before the era of retrograde approach, the ostial LAD CTO was remain an untouch-

able territory due to very low success rate and high complication rate. To our best knowledge, there have been no previously reported suitable predictors of successful ostial LAD CTO PCI. Thus, our aim of the study was to fill this gap and determine possible predictors for the success of ostial LAD CTO PCI. METHODS Patient Enrollment and Exclusion Criteria

This retrospective study protocol was approved by the Kaohsiung Chang Gung Memorial Hospital in Taiwan’s Institutional Review Board. All patients gave their written informed consent prior to participation in the study. CTO was defined as thrombolysis of myocardial infarction grade (TIMI) 0 for more than 3 months, with the presence of typical angina or reversible myocardial ischemia on a thallium stress study. Exclusion criteria were: (1) recent myocardial infarction (MI) or unstable hemodynamics; (2) total occlusion of bypass grafts. During the period from January 2001 to September 2013, 621 consecutive patients who underwent PCI for CTO of a native coronary artery were included. Seventy patients underwent ostial LAD CTO PCI, 551 patients underwent all other CTOs PCI. The baseline demographics, angiographic characteristics, and procedural outcomes were compared in both groups. All procedural coronary angiograms were reviewed to assess the anatomy and morphology of the CTO segment and grade of collaterals. Operator Selection The CTO intervention procedures were limited to one experienced operators in our institution. The experienced operator met the criteria of “CTO operators” who had specific proctored experience of more than 100 CTOs [23]. Definitions

Ostial LAD CTO was defined as CTO at the position whose distance between lesion and left main bifurcation was less than 1 mm. The duration of occlusion was estimated by a history of angina, history of MI in

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the same territory, or previous angiography. The characteristics of each CTO lesion were defined according to the Syntax Scoring system based on the complexity of the coronary artery disease. Severe calcification of a CTO lesion was defined as multiple persisting opacifications of the coronary wall being visible in more than one projection surrounding the complete lumen of the coronary artery at the site of the lesion. Severe tortuosity was defined as there being one or more bends of    90 or more, or three or more bends of 45 –90 proximal of the diseased segment. Good collateral circulation was defined as TIMI 3 collateral flow. Length of the CTO was measured following bilateral simultaneous coronary injections in cases with collaterals from other coronary arteries, or antegrade coronary injection in cases with bridging collaterals, visualizing the filling of both proximal and the distal occluded artery. Antegrade failure was defined as the antegrade guide-wire not being able to enter into the CTO segment. The retrograde approach was defined as the introduction of the guide-wire into the collateral channels (CCs), which are connected to the target CTO vessel distal to the lesion. Retrograde success was defined as the retrograde guide-wire successfully entering into the distal portion of the CTO segment. Angiographic success was defined as residual stenosis 30% by visual analysis in the presence of grade TIMI 3 flow. In addition, the distal wire position was documented to be in the true lumen by either a coronary angiogram or intravascular ultrasound (IVUS) examination. Coronary Angiogram, IVUS, Syntax Score, and J-CTO Score Interpretation All coronary angiograms and IVUS were independently interpreted by a cardiologist who was blinded to the procedure. Syntax Score and J-CTO score were sent to a blinded and independent core angiographic laboratory to analyze the scores. Medications and Other Interventional Materials

Each patient was pretreated with aspirin and clopidogrel and administered weight-adjusted heparin to keep the activated clotting time (ACT) more than 250 sec each hour. During the interventional procedure, either Iohexol, a nonionic, iodinated, low osmolar radiologic contrast agent, or iodixanol (Visipaque, 320 mg iodine/ml, Amersham Health, Princeton, NJ) a nonionic, iso-smolar (290 mOsm/kg water) contrast agent was used. Serum creatinine was measured at 24 hr before the procedure and between 48 and 72 hr after the procedure. Additional serum creatinine measurements were obtained in patients with initial elevation of serum creatinine or post-procedural deterioration of

baseline renal function or in patients with prolonged hospitalization for other reasons, such as hemorrhage or ischemia. The guide-wires used included Ultimate Bros 3g (Asahi, Japan), Miracle 3g (Asahi, Japan), Miracle 6g (Asahi, Japan), Miracle 9g (Asahi, Japan), Conquest (Asahi, Japan), and Conquest Pro (Asahi, Japan) called stiff-wires. Microcatheters included transit catheters (Cordis), finecross catheters (Terumo, Japan), and the Ryujin over-the-wire balloon (Terumo, Japan). Statistical Analysis Baseline patient characteristics, angiographic data, and parameters during each procedure were compared between patients who received ostial LAD CTO PCI and those who received all other CTOs PCI. Variables were reported as mean 6 SD for continuous variables or as percentages for categorical variables. The chisquare test was used for categorical variables, and Student’s t test was used for continuous variables. Predictors of successful PCI to ostial LAD CTO were independently analyzed according to three groups of clinical, procedural, and angiographic variables. Stepwise univariate logistic regression analysis was also performed for the identification of possible significant predictors. We included to our multivariable analysis parameters that were found to exhibit significant difference in the univariate logistic analysis. A P level < 0.05 was considered statistically significant for all calculations. Statistics were performed using SPSS 15.0 (SPSS, Chicago, IL). RESULTS Population Demographics

A total of 621 patients were enrolled in this study, with 70 patients undergoing ostial LAD CTO PCI and 551 patients undergoing all other CTOs PCI. The baseline clinical characteristics are detailed in Table I. When comparing with ostial LAD CTO PCI patients and all other CTOs PCI patients, we found that there was no significant difference between the age, age > 75, male gender, body weight, and body height. Creatinine level was also similar in both groups. Although hyperlipidemia was found to be more prevalent in the all other CTOs PCI group (64.6% vs. 48.6%, P ¼ 0.009), the rest of the risk factors were similar between groups, such as diabetes mellitus, hypertension, and current smoker. Furthermore, the incidence of comorbidities including previous MI, previous CABG history, previous stroke, peripheral vascular disease (PVD), and end stage renal disease (ESRD) was similar between groups. The left ventricular

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

The Predictor of Successful PCI to Ostium LAD CTO TABLE I. Baseline Demographic Characteristics in Ostial LAD CTO Group and All Other CTOs Group

Demographics Age, years Age > 75 Male Body Weight, kg Body Height, cm Creatinine, mg/dl Risk factors Diabetes mellitus Hypertension Current Smoker Cholesterol >200 mg/dl Co-morbidity Previous MI Previous CABG Previous stroke PVD ESRD LVEF (%)

TABLE II. Angiographic Characteristics, Interventional Procedure and PCI Result in Ostial LAD CTO Group and All Other CTOs Group

Ostial LAD CTO (n ¼ 70)

All other CTOs (n ¼ 551)

P

60.9 6 11.0 5 (7.1) 60 (85.7) 67.5 6 13.3 163.4 6 7.2 1.4 6 1.8

62.8 6 11.2 65 (11.8) 472 (85.7) 69.5 6 12.2 162.6 6 7.7 1.4 6 1.6

0.180 0.246 0.991 0.199 0.453 0.704

19 55 34 34

(27.1) (78.6) (48.6) (48.6)

28 (40.0) 5 (7.1) 10 (14.3) 1 (1.4) 2 (2.9) 56.8 6 15.7

211 391 252 356

(38.3) (71.0) (45.7) (64.6)

172 (31.2) 30 (5.4) 89 (16.2) 22 (4.0) 18 (3.3) 56.6 6 14.6

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0.069 0.183 0.654 0.009 0.138 0.562 0.688 0.285 0.855 0.914

*Data are presented as mean 6 SD or number (%) of patients. LAD, left anterior descending artery; CTO, chronic total occlusion; MI, myocardial infarction; CABG, coronary artery bypass graft; PVD, peripheral vascular disease; ESRD, end stage renal disease; LVEF, left ventricle ejection fraction.

ejection fraction (LVEF) was also similar between ostial LAD CTO PCI group and all other CTOs PCI group (56.8 6 15.7 vs. 56.6 6 14.6; P ¼ 0.914). Lesion and Procedural Characteristics (J CTO Score and Syntax Score)

The characteristics of coronary artery and CTO lesions are shown in Table II. The incidence of CTO target lesions was predominantly in the left anterior descending (LAD) (39.2%) and right coronary artery (RCA) (43.6%) in the all other CTOs group. The incidence of in-stent CTO lesions was slightly lower in the ostial LAD CTO PCI group, but without significant statistical difference (7.1% in the ostial LAD CTO PCI group vs. 13.2% in the all other CTOs PCI group, P ¼ 0.147). Because of the specific position of the ostial LAD CTO, the incidence of side branch occlu sion and bending >45 was significantly higher in the ostial LAD CTO PCI group (100.0% vs. 36.1%, P < 0.001; 87.1% vs. 75.9%, P ¼ 0.034). The ostial LAD CTO PCI group also had a higher incidence of good collaterals (88.6% vs. 62.3%, P ¼ 0.001) as well as a higher incidence of severe calcification, blunt stump or no stump, and bridging collaterals, but without significant difference. J-CTO score and Syntax Score were significantly higher in the ostial LAD CTO PCI group (2.7 6 0.8 vs.

Ostial LAD CTO (n ¼ 70) Target CTO vessel LAD LCX RCA Condition of target lesion De novo In-stent Angiographic findings Side branch at occlusion (>1.5 mm)  Bending >45 Severe calcification Blunt stump or no stump Good collaterals Bridging collaterals Lesion length (mm) J CTO Score J CTO Score >2 J CTO Score >3 Syntax Score Syntax Score >22 Syntax Score >33 PCI procedure Ad hoc PCI Staged PCI Procedure duration (min) Fluoroscopic time (min) Contrast volume (ml) Contralateral injection Retrograde approach IVUS guided PCI Contrast induced nephropathy Final Success

All other CTOs (n ¼ 551)

P NS

70 (100.0) 0 (0.0) 0 (0.0)

216 (39.2) 95 (17.2) 240 (43.6)

65 (92.9) 5 (7.1)

478 (86.8) 73 (13.2)

0.147

70 (100.0)

199 (36.1)

0.000

61 (87.1) 26 (37.1) 33 (47.1) 62 (88.6) 35 (50.0) 38.1 6 18.9 2.7 6 0.8 42 (60.0) 10 (14.3) 28.3 6 6.5 51 (72.9) 14 (20.0)

418 (75.9) 177 (32.1) 249 (45.2) 343 (62.3) 212 (38.5) 34.5 6 15.5 2.2 6 1.1 211 (38.3) 61 (11.1) 20.9 6 9.7 218 (39.6) 52 (9.4)

0.034 0.399 0.757 0.000 0.063 0.092 0.011 0.000 0.426 0.000 0.000 0.005 0.000

23 (32.9) 47 (67.1) 134.2 6 57.4 61.0 6 33.2 381.4 6 205.3 36 (51.4) 29 (41.4) 53 (75.7) 3 (4.3) 56 (80.0)

445 (80.8) 106 (19.2) 101.4 6 47.2 41.6 6 24.9 279.2 6 128.0 94 (17.1) 65 (11.8) 128 (23.2) 26 (4.7) 451 (81.9)

0.000 0.000 0.000 0.000 0.000 0.000 0.872 0.706

*Data are presented as mean 6 SD or number (%) of patients. PCI indicates percutaneous coronary intervention; LAD, left anterior descending artery; CTO, chronic total occlusion; LCX, left circumflex artery; RCA, right coronary artery; IVUS, intra-vascular ultrasound.

2.2 6 1.1, P ¼ 0.011; 28.3 6 6.5 vs. 20.9 6 9.7, P < 0.001). The incidence of the J-CTO scores that were more than 2 was significantly higher in the ostial LAD CTO PCI group (60.0% vs. 38.3%, P < 0.001) but without significant difference when the incidence of J-CTO scores more than 3 (14.3% vs. 11.1%, P ¼ 0.426). Syntax Scores more than 22 and more than 33 were similar with the J-CTO score with a higher incidence in the ostial LAD CTO PCI group (72.9% vs. 39.6%, P < 0.001; 20.0% vs. 9.4%, P ¼ 0.005). All interventional procedural characteristics are also listed in Table II. Staged PCI procedure was predominantly given to the ostial LAD CTO PCI group (67.1% vs. 19.2%, P < 0.001). The procedure duration and fluoroscopic time were significantly longer in the ostial

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LAD CTO PCI group than in the all other CTOs PCI group (134.2 6 57.4 vs. 101.4 6 47.2, P < 0.001; 61.0 6 33.2 vs. 41.6 6 24.9, P < 0.001). The contrast volume was also higher in the ostial LAD CTO PCI group than in the all other CTOs PCI group (381.4 6 205.3 vs. 279.2 6 128.0, P < 0.001). There was also a significantly higher incidence of the approach manner used (contralateral injection, retrograde approach, and IVUS guided PCI) in the ostial LAD CTO PCI group (51.4% vs. 17.1%, P < 0.001; 41.4% vs. 11.8, P < 0.001; 75.7% vs. 23.2%, P < 0.001). In addition, the frequency of contrast induced nephropathy was similar between groups. The incidence of final procedure success was also similar between groups (80.0% vs. 81.9%, P ¼ 0.706). Predictor Evaluation

Predictors of successful PCI for ostial LAD CTO were independently analyzed according to three groups of clinical, procedural, and angiographic variables. Stepwise univariate logistic regression analysis was also performed and the possible significant predictors are summarized in Table III. There were no significant differences between groups (success vs. failure) in baseline characteristics such as gender, age, body weight, body height, hypertension, diabetes mellitus, dyslipidemia, and current smoking. There were also no significant differences between groups in comorbidities including history of MI, history of stroke, history of peripheral vascular disease, and left ventricular ejection fraction. In angiographic characteristics, there were no significant differences in stump morphology (tapper, blunt, or no stump), calcified degree, collaterals (good or bridging), lesion length, lesion length more than 20 mm, and history of previous re-do. In Table III, it can be seen that there is no significant differences between groups without involving LM or without involving ostial LCX. Staged PCI was also not a predictor for successful PCI to ostial LAD CTO. There were no significant differences in J-CTO score or J-CTO score 75 vs. Age  75 Body weight (kg)a Body height (cm)a Hypertension Diabetes mellitus Current smoking Dyslipidemia Prior MI Prior stroke Prior PVD LVEF (%)a Blunt stump Tapper stump No stump Severe calcification Good collaterals Bridging collaterals Lesion length (mm)a Lesion length 20 (mm) Previous re-do Without involve LM Without involve ostial LCX Staged PCI J CTO scorea J CTO score 45%], : : :etc.) than all other CTOs but with better good collaterals (88.6% vs. 62.3%, P < 0.001). The major differences between ostial LAD CTO and all the other CTOs were found to be angiographically difficult but with better retrograde chances. The possibility of encountering angiographically difficulties was found to be almost the same high in ostial LAD CTO group thus mimicking the prediction of success or failure in ostial LAD CTO PCI. Comparison Between Ostial LAD CTO PCI and All Other CTOs PCI

The Ostial LAD lesion has been considered as a special coronary artery site due to its importance in coronary arteries and its anatomical differences. Several publications have thus focused on the treatment strategies such as bare-metal stents versus drug-eluting stents, just ostial stenting versus cross-over to left main artery stenting [28,29]. The specific conditions in ostial LAD CTO involve its anatomical differences of the presence of the largest side branch (left circumflex artery), higher incidence of blunt stump or without stump,  and tendency for bending more than 45 but with better retrograde of intracoronary collaterals. Our study found these basic coronary anatomic differences and revealed that ostial LAD CTO also combined with more complex lesion morphology when using Syntax Score and J-CTO score for analysis (28.3 6 6.5 vs. 20.9 6 9.7, P < 0.001; 2.7 6 0.8 vs. 2.2 6 1.1, P ¼ 0.011). The procedure was also more difficult with longer procedural duration, fluoroscopic time, and contrast volume when performing

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PCI to ostial LAD CTO. However, new devices and techniques like the retrograde approach, contralateral injection, and IVUS guide have helped to make ostial LAD CTO more accessible. Predictor of Final Successful Ostial LAD CTO PCI Our initial intention was to find a predictor of successful PCI for ostial LAD CTO before the procedure using the J-CTO score, Syntax Score and other angiographic findings. Only Syntax Score was found to progress to the multivariate analysis, which revealed it as a negative predictor. Although J-CTO score was higher in the ostial LAD CTO PCI group, it could not become a predictor of successful PCI for ostial LAD CTO after analysis. These findings reveal that one of the most difficult CTO PCI was at ostial LAD and the possibility of success lay primarily during the procedure. The Syntax Score for Ostial LAD CTO PCI Prediction Syntax Score was first developed as a grading tool for the complexity of coronary artery disease [17]. And while the 3-year and 5-year Syntax trial outcome revealed that Syntax Score was a risk category system for guiding interventionists to perform PCI or CABG [18,19], no clinical trial has used Syntax Score for predicting successful CTO PCI. Our study confirms that Syntax Score is a negative predictor for successful ostial LAD CTO PCI. Conversely, when we classified Syntax Score

The predictors of successful percutaneous coronary intervention in ostial left anterior descending artery chronic total occlusion.

Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) has become one of the treatment strategies in recent era. The ostium of the ...
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