Percutaneous Coronary Intervention of Chronic Total Occlusions in Patients With Low Left Ventricular Ejection Fraction

JACC: CARDIOVASCULAR INTERVENTIONS

VOL.

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

-, NO. -, 2017

ISSN 1936-8798/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jcin.2017.06.058

Percutaneous Coronary Intervention of Chronic Total Occlusions in Patients With Low Left Ventricular Ejection Fraction Alfredo R. Galassi, MD,a,b Marouane Boukhris, MD,a,c Aurel Toma, MD,d Zied Ibn Elhadj, MD,c Lobna Laroussi, MD,c Oliver Gaemperli, MD,b Michael Behnes, MD,d Ibrahim Akin, MD,d Thomas F. Lüscher, MD,b Franz J. Neumann, MD,d Kambis Mashayekhi, MDd

ABSTRACT OBJECTIVES The study sought to assess the outcome of percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) in patients with low left ventricular ejection fraction (LVEF) (#35%). BACKGROUND Data regarding the outcome of PCI in patients with low LVEF affected by CTO are scarcely reported. METHODS The authors performed a prospective longitudinal multicenter study including consecutive patients undergoing elective PCI of CTOs. Patients were subdivided into 3 groups: group 1 (LVEF $50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF #35%). RESULTS A total of 839 patients (mean 64.6
10.5 years of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF #35% was present in 72 (8.6%) patients. The angiographic success was high (overall 93.6%) and similar among the 3 groups (93.5% vs. 94.4% vs. 91.7%, respectively; all p ¼ NS). In group 3, no periprocedural complications of CTO PCI were observed. Mean clinical follow-up of 16.3
8.2 months duration was available in 781 (93.1%) patients including those with LVEF #35%. At 2 years, major cardiac and cerebrovascular events (MACCE) free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p ¼ NS). In patients with LVEF #35%, LVEF improved significantly in the presence of a successful CTO PCI from 29.1
3.4% to 41.6
7.9% (p < 0.001). CONCLUSIONS In CTO patients with low LVEF, PCI could represent a safe and effective revascularization strategy achieving good midterm outcome and LVEF improvement. (J Am Coll Cardiol Intv 2017;-:-–-) © 2017 by the American College of Cardiology Foundation.

C

oronary chronic total occlusion (CTO) repre-

artery disease, CTO was the strongest independent

sents a frequent lesion subset observed in

predictor of incomplete percutaneous revasculariza-

about 15% of patients undergoing coronary

tion, and associated with adverse clinical outcomes

angiography (1–3), with a higher prevalence in those

with

previous

coronary

artery

bypass

(7–9).

grafting

On the other hand, left ventricular ejection fraction

(CABG) (1,4). The presence of a CTO confers a nega-

(LVEF) represents one of the strongest predictors of

tive impact on long-term outcome in different clinical

cardiovascular events in patients with coronary ar-

situations. Indeed, in patients experiencing an acute

tery disease (10). Very recently, it has been shown

coronary syndrome, a coexisting CTO is associated

that

with increased early and late mortality (5,6). Simi-

(LVEF #35%), the presence of CTO was related to

larly, in the setting of stable multivessel coronary

worse long-term outcome (11). Although PCI might

in

patients

with

ischemic

From the aDepartment of Experimental and Clinical Medicine, University of Catania, Catania, Italy; bUniversity Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland; cCardiology Department, Abderrhamen Mami Hospital, Ariana, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; and the dDivision of Cardiology and Angiology II, University Heart Center Freiburg – Bad Krozingen, Bad Krozingen, Germany. Dr. Lüscher has received research and educational grants from AstraZeneca, Biotronik, Eli Lilly, Medtronic, Boston Scientific, Abbott, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received February 21, 2017; revised manuscript received June 26, 2017, accepted June 29, 2017.

heart

failure

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CTO PCI and Low LVEF

ABBREVIATIONS

often remain the last available option to

angiographic success with no periprocedural compli-

AND ACRONYMS

manage patients with low LVEF, outcome

cations including cardiac death, Q-wave and non–Q-

data of percutaneous recanalization of CTO

wave myocardial infarction (MI), tamponade, stroke,

subtending viable myocardium in this subset

and need for emergency CABG. Coronary perforations

of patients are scarcely reported.

were defined and described as previously shown (14).

bSS = baseline SYNTAX score CABG = coronary artery bypass grafting

CTO = chronic total occlusion HR = hazard ratio LVEF = left ventricular ejection fraction

MACCE = major adverse

Accordingly, we aimed to assess the

In all patients, creatine kinase-myocardial band was

impact of LVEF on success rates and in-

evaluated 6 h after the procedure and until normali-

hospital outcome of CTO PCI, and to eval-

zation if the levels were abnormal. Non–Q-wave MI

uate the midterm outcome of patients with

was defined as creatine kinase-myocardial band

low LVEF treated by PCI for a CTO.

enzyme elevation >3 times the upper limit of normal

METHODS

requiring pericardiocentesis. Major bleeding was

(9). Tamponade was defined as an epicardial effusion

cardiac and cerebrovascular events

defined according to Acuity criteria (15).

MI = myocardial infarction

In patients with LVEF #35%, the baseline SYNTAX

OR = odds ratio

STUDY POPULATION. We performed a pro-

PCI = percutaneous coronary

spective

including

score (bSS) and the residual SYNTAX score (rSS) (after

intervention

consecutive patients undergoing elective PCI

achieving the target level of revascularization) were

rSS = residual SYNTAX score

of CTO at 3 European centers from January

determined. SYNTAX Revascularization Index (SRI)

SRI = SYNTAX

2013 to December 2015 (Online Figure 1). All

was then calculated using the following formula:

Revascularization Index

procedures were scheduled (not ad hoc PCI),

SRI ¼ (bSS  rSS)/bSS  100 (16).

TVR = target vessel

and performed by experienced CTO opera-

At follow-up, major adverse cardiac and cerebro-

revascularization

tors. Patients were selected on the basis of

vascular events (MACCE) were defined as the com-

the presence of symptoms, viability, and inducible

posite of cardiac death, MI, stroke and further

ischemia (>10%) in the CTO artery territory, as

revascularization (CTO target vessel revascularization

demonstrated by functional imaging tests. In pres-

[TVR] or non-TVR).

multicenter

study

ence of impaired LVEF, CTO revascularization was only

considered

for

lesions

subtending

viable

myocardial territory judged to be of hemodynamic importance. The decision of the revascularization strategy (PCI or CABG, and lesions to be revascularized) for each patient was left to the local heart team in the participating center. In case of surgical indication rejected by the patient, PCI was proposed if considered to be feasible by the local heart team. According to the LVEF, our study population was subdivided into 3 groups: group 1 (LVEF $50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF #35%). The study was carried out in accordance to the Helsinki declaration; all patients provided written informed consent. DEFINITIONS AND ENDPOINTS. Coronary CTOs were

defined as angiographic evidence of total occlusions with Thrombolysis In Myocardial Infarction flow grade 0 within a major epicardial coronary artery of at least 2.5 mm, and estimated durations of at least 3 months (12). The complexity of CTO lesion and the difficulty of CTO PCI attempt were assessed according to the J-CTO (Japanese multicenter registry) score and the ORA (O ¼ ostial, R ¼ filling < Rentrop 2, A ¼ age $75 years) score, respectively (8,13). Angiographic

INTERVENTIONAL

PROCEDURES. Arterial

access

was usually established via right or left femoral arteries. The size of the guiding catheters used for the occluded artery was 7-F in the majority of cases. Dual injection was considered routinely if contralateral collaterals were present. The sequence of use of wiring techniques, the guidewire selection and the primary CTO strategy (antegrade, retrograde, or hybrid) was completely left to the operator’s discretion, as well as the use of percutaneous mechanical circulatory support. Patients received an initial bolus of intravenous unfractionated heparin (100 IU/kg). The activated clotting time was monitored every 30 min to determine if an additional bolus of unfractionated heparin was necessary to maintain an activated clotting time >350 s. Upstream use of glycoprotein IIb or IIIa inhibitor therapy or bivalirudin was avoided. In patients with LVEF #35%, we aimed to perform functional revascularization in 1 PCI procedure or in a staged manner during the same hospitalization, to achieve the lowest possible rSS. Only drug-eluting stents were implanted. Antiplatelet therapy and heart failure medication (if necessary) were prescribed according to recognized standard of care (17,18).

success was defined as final residual stenosis <30%

BASELINE SYMPTOMS EVALUATION. Dyspnea and

(by visual estimation) and TIMI flow grade 3 after CTO

angina

recanalization. Clinical success was defined as an

Heart Association functional class and Canadian

were

assessed

according

to

New

York

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CTO PCI and Low LVEF

F I G U R E 1 Flowchart of the Study Population

The overall prevalence of CTO patients with low LVEF was 8.6%. The angiographic success rate in this subset of patients was 91.7%. CTO ¼ chronic total occlusion; LVEF ¼ left ventricular ejection fraction; PCI ¼ percutaneous coronary intervention.

Cardiovascular Society class, respectively, before the

STATISTICAL ANALYSIS. Continuous variables were

indexed CTO procedure.

presented as mean
SD, and were compared using

BASELINE LVEF AND VIABILITY ASSESSMENT. A

2-dimensional echocardiogram was performed in all patients 48 to 72 h before CTO PCI attempt. LVEF was assessed by Simpson’s biplane method. In presence of normal wall motion or hypokinesia in the territory subtended by the CTO artery, no further viability testing was performed, whereas in patients with akinesia or dyskinesia in CTO territory, assessment of viability was performed by myocardial scintigraphy or magnetic resonance imaging (19).

the unpaired Student t test. Categorical variables were presented as counts and percentage and compared using the chi-square test when appropriate (expected frequency >5); otherwise, the Fisher exact test was used. The predictors of the angiographic success were identified using a logistic regression. All clinical and angiographic characteristics were tested. All univariate variables with a p < 0.10 were included in a statistical model to detect the independent predictors using multivariate regression analysis with the Wald method.

FOLLOW-UP DATA. Clinical follow-up was obtained

MACCE-free survival during follow-up was evalu-

either by a clinical visit or by a telephone interview.

ated according to the Kaplan-Meier method and

Details regarding MACCE occurrence were addition-

compared between successful and failed CTO PCI

ally collected by the physicians through the revision

using the log-rank test. Univariate Cox regression was

of clinical source documentation. Symptoms (angina

used to assess the impact of percutaneous mechanical

and dyspnea) were reassessed at 6 months.

circulatory support use and that of SRI $70% on

In patients with LVEF #35% who underwent

MACCE occurrence in CTO patients with LVEF #35%.

successful CTO PCI, LVEF was assessed at 6

Univariate analyses were performed, and multivar-

months. In this latter subset of patients, repeat

iate Cox proportional hazards regression modeling

angiography was scheduled between 8 and 12

using purposeful selected covariates was applied to

months, unless previously clinically indicated.

determine the independent predictors of long-term

Reocclusion was defined as a TIMI flow grade 0 to 1

MACCE occurrence in all population. All univariate

in the target CTO vessel, whereas restenosis was

variables with p values <0.10 were included in the

defined as >50% luminal narrowing at the segment

model. Variables judged to be of clinical importance

site including the stent and 5 mm proximal and

from previous published research were included

distal to the stent edges.

in the multivariate model-building process despite

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CTO PCI and Low LVEF

T A B L E 1 Clinical Characteristics of the Study Population

All (N ¼ 839)

LVEF $50% (n ¼ 552) (Group 1)

LVEF 35%–50% (n ¼ 215) (Group 2)

LVEF #35% (n ¼ 72) (Group 3)

64.6
10.5

63.8
10.2

65.8
11.3*

66.4
10.0

$75 years of age

163 (19.4)

85 (15.4)

58 (27.0)*

20 (28.8)†

Males

736 (87.7)

475 (86.1)

195 (90.7)

66 (91.7)

Diabetes

252 (30.0)

152 (27.5)

67 (31.2)

33 (45.8)†‡

Smoker

447 (53.3)

289 (52.4)

116 (54)

42 (58.3)

Hypertension

695 (82.8)

455 (86.1)

179 (83.3)

61 (84.7)

Dyslipidemia

607 (72.3)

385 (69.7)

174 (80.9)*

48 (66.7)†‡

BMI, kg/m2

28.6
4.5

28.6
4.5

28.9
4.4

27.3
4.2‡

Peripheral artery disease

129 (15.4)

66 (12)

46 (21.4)*

17 (23.6)†

Chronic kidney disease

130 (15.5)

68 (12.3)

44 (20.5)*

18 (25)†

Prior MI

358 (42.7)

197 (35.7)

118 (54.9)*

43 (59.7)†

Prior PCI

287 (34.2)

186 (33.7)

84 (39.1)

17 (23.6)‡

Prior CABG

141 (16.8)

77 (13.9)

50 (23.3)*

14 (19.4)

Prior stroke

13 (1.5)

6 (1.1)

5 (2.3)

2 (2.8)

370 (44.1)

211 (38.2)

117 (54.4)*

42 (58.3)†

40 (4.7)

18 (3.2)

13 (6.9)*

9 (12.5)†

175 (20.8)

91 (16.5)

61 (28.4)

23 (31.9)

Age, yrs

3-vessel disase >1 CTO

†‡

Angina (CCS class) No angina I

87 (10.4)

54 (9.8)

26 (12.1)

7 (9.7)

II

266 (31.7)

185 (33.5)

62 (28.8)

19 (26.4)

III

270 (32.2)

203 (36.8)

54 (25.1)

13 (18.1)

IV

41 (4.9)

19 (3.4)

12 (5.6)

10 (13.9)

I

252 (30.1)

190 (34.4)

54 (25.1)

8 (11.1)

II

274 (32.6)

194 (35.2)

65 (30.2)

15 (20.8)

III

275 (32.8)

165 (29.9)

74 (34.5)

36 (50.0)

IV

38 (4.5)

3 (0.5)

22 (10.2)

13 (18.1)

†‡

Dyspnea (NYHA functional class)

Values are mean
SD or n (%). *Group 1 vs. group 2, p < 0.05. †Group 1 vs. group 3, p < 0.05. ‡Group 2 vs. group 3, p < 0.05. BMI ¼ body mass index; CABG ¼ coronary artery bypass grafting; CCS ¼ Canadian Cardiovascular Society; CTO ¼ chronic total occlusion; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; NYHA ¼ New York Heart Association; PCI ¼ percutaneous coronary intervention.

T A B L E 2 Angiographic Characteristics

All CTO PCI (N ¼ 839)

LVEF $50% CTO PCI (n ¼ 552) (Group 1)

LVEF 35%–50% CTO PCI (n ¼ 215) (Group 2)

LVEF #35% CTO PCI (n ¼ 72) (Group 3)

LAD

222 (26.5)

LCx

123 (14.7)

151 (27.4)

55 (25.6)

16 (22.2)

76 (13.9)

30 (14.0)

RCA

17 (23.6)

494 (58.9)

325 (58.9)

130 (60.4)

39 (54.2)

Blunt stump

506 (60.3)

330 (59.8)

126 (58.6)

50 (69.4)

Bending >45

265 (31.6)

180 (32.6)

64 (29.8)

21 (29.2)

Severe calcifications

234 (27.9)

155 (28.1)

59 (27.4)

20 (27.8)

CTO length, mm

42.2
29.2

42.6
29.6

42.5
29.0

39.0
27.3

CTO length $20 mm

674 (80.3)

441 (79.9)

179 (83.3)

56 (77.8)

Ostial location

111 (13.2)

68 (12.3)

31 (14.4)

12 (16.7)

In-stent CTO

56 (6.7)

33 (6.0)

15 (7.0)

8 (11.1)

255 (30.4)

190 (34.4)

49 (22.8)

16 (22.2)* 38 (52.8)*†

Target CTO artery

Previous attempt Collateral filling, Rentrop grades 2–3

574 (68.4)

388 (70.3)

148 (68.8)

J-CTO score $3

402 (47.9)

273 (49.5)

97 (45.1)

32 (44.4)

ORA score $3

103 (12.3)

53 (9.6)

35 (16.3)‡

15 (20.8)*

Values are n (%) or mean
SD. *Group 1 vs. group 3, p < 0.05. †Group 2 vs. group 3, p < 0.05. ‡Group 1 vs. group 2, p < 0.05. J-CTO ¼ Japanese multicenter registry; LAD ¼ left anterior descending; LCx ¼ left circumflex; ORA ¼ O: ostial; R: filling < Rentrop 2; A: age $75 years; RCA ¼ right coronary artery; other abbreviations as in Table 1.

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F I G U R E 2 Success Rate and Procedural Details According to LVEF

(A) Angiographic and clinical success rates according to left ventricular ejection fraction (LVEF). (B) Successful antegrade and retrograde approaches according to LVEF. (C) Antegrade/retrograde (A/R) wire escalation and A/R) dissection re-entry techniques according to LVEF. (D) Stiffness of guidewires crossing the CTOs (into true lumen) according to LVEF.

p values >0.1. A p value <0.05 was considered to

In comparison with patients with preserved LVEF

indicate statistical significance. All data were pro-

(group 1), those with low LVEF (group 3) had more

cessed using SPSS version 21 (IBM Corporation,

comorbidities

Armonk, New York).

disease, chronic kidney disease; all p < 0.05), more

(e.g.,

diabetes,

peripheral

artery

previous MI (59.7% vs. 37.5%; p < 0.001) and showed

RESULTS

more frequent 3-vessel coronary artery disease (58.3% vs. 38.2%; p < 0.001). Group 3 patients were more often

CTO PCI was attempted in a total of 839 patients

diabetic (45.8% vs. 31.2%; p ¼ 0.018) and had under-

(mean 64.6
10.5 years of age, 87.7% men). Accord-

gone less prior PCI (23.6% vs. 39.1%; p ¼ 0.012) in

ing to baseline LVEF, the study population was sub-

comparison with group 2. Table 1 summarized the

divided as follows: group 1 (LVEF $50%) 552 (65.8%)

clinical characteristics of the study population. CTO

patients; group 2 (LVEF 35% to 50%) 215 (25.6%) pa-

patients with LVEF #35 complained more often of se-

tients; and group 3 (LVEF #35%) 72 (8.6%) patients

vere dyspnea and less often of angina than did those

(Figure 1).

with preserved or mildly impaired LVEF (all p < 0.05).

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CTO PCI and Low LVEF

T A B L E 3 Procedural Details

All CTO PCI (N ¼ 839)

LVEF $50% CTO PCI (n ¼ 552) (Group 1)

2.5
1.3

2.5
1.4

Stent length, mm

70.4
37.8

66.8
36.3

78.6
40.7*

Procedural time, min

118.1
75.5

119.0
75.3

118.1
79.2

57.1
39.2

57.0
38.2

57.9
43.0

358.0
206.5

369.9
213.9

349.1
197.7

3497.2
2539.0

3578.8
2574.6

3341.9
2299.4

Number of DES

Fluoroscopy time, min Contrast load, ml Air kerma radiation exposure, mGy

LVEF #35% CTO PCI (n ¼ 72) (Group 3)

LVEF 35%–50% CTO PCI (n ¼ 215) (Group 2)

2.7
1.7

2.4
1.3 73.4
36.9 110.5
61.9 54.8
35.3 295.6
159.0†‡ 3335.3
2854.6

Values are mean
SD. *Group 1 vs. group 2, p < 0.05. †Group 1 vs. group 3, p < 0.05. ‡Group 2 vs. group 3, p < 0.05. DES ¼ drug-eluting stent(s); other abbreviations as in Table 1.

The rate of previously failed CTO procedures that

myocardial scintigraphy and magnetic resonance

were reattempted in our study population was lower

imaging in 15 (20.8%) and 17 (23.6%) patients,

in patients with low LVEF (#35%) than in those pa-

respectively, whereas in the remaining 40 (55.6%)

tients with preserved LVEF (22.2% vs. 34.4%; p ¼

patients 2-dimensional echocardiography revealed

0.024). Although J-CTO score was similar in the 3

hypokinesia in CTO territory. Figure 3 illustrates the

groups (J-CTO score $3: 49.5% vs. 45.1% vs. 44.4%;

distribution of coronary artery disease within the 3

all p ¼ NS), CTO PCI attempts were considered to be

major epicardial vessels, in patients with low LVEF.

more difficult in group 3 in comparison with group 1,

Percutaneous mechanical circulatory support devices

as assessed by the ORA score (ORA score $3: 20.8%

were used in 10 (13.8%) patients: intra-aortic balloon

vs. 9.6%; p ¼ 0.006) (Table 2).

pump in 8 cases and extracorporeal membrane

The angiographic success was high (overall 93.6%)

oxygenation in 2 cases. In patients with LVEF #35%

and similar among the 3 groups (93.5% vs. 94.4% vs.

who underwent successful CTO PCI, an rSS of 11.5


91.7%; all p ¼ NS), as well as the clinical success (92%

4.1 (bSS 36.5
18.3) was obtained (Figure 3B); and an

vs. 92.1% vs. 91.7%; all p ¼ NS) (Figure 2A). Similar

SRI $70% was achieved in 48 (72.7%) patients. Except

success rate was achieved among the 3 participating

3 cases of type I perforation (Ellis classification), no

centers (Online Figure 1). Multivariate analysis iden-

other periprocedural complications of CTO PCI at-

tified female sex (odds ratio [OR]: 2.64; 95% confi-

tempts

dence interval [CI]: 1.17 to 5.99; p ¼ 0.02, J-CTO

LVEF #35% (Table 4).

were

observed

in

CTO

patients

with

score $3 (OR: 8.26; 95% CI: 3.77 to 18.08; p < 0.001),

Clinical follow-up was available in 781 (93.1%) pa-

and ORA score $3 (OR: 4.09; 95% CI: 1.77 to 9.47; p ¼

tients, including all those with LVEF #35% (mean

0.001) as independent predictors of angiographic

follow-up period 16.3
8.2 months). In patients with

failure, whereas LVEF #35% was not associated with

LVEF #35% successfully revascularized, only 1 car-

failure (OR: 1.43; 95% CI: 0.55 to 3.70; p ¼ 0.464).

diac death (1.5%) was observed in a 75 year-old dia-

The use of antegrade and retrograde approaches

betic man with 2-vessel disease who underwent

was similar between the 3 groups, and no difference

successful antegrade CTO PCI of the proximal left

was observed in terms of using conventional wire

circumflex artery, then staged PCI of the left anterior

escalation and dissection re-entry techniques (all p ¼

descending artery 3 days later. The patient experi-

NS) (Figures 2B and 2C). Furthermore, in successfully

enced sudden cardiac death 7 days after discharge.

recanalized patients, the stiffness of guidewires

Two noncardiac deaths were also noticed due to

crossing the CTO lesions was similar between the 3

gastrointestinal

groups (Figure 2D).

Among patients with failed CTO attempts, 2 (with left

bleeding

and

renal

carcinoma.

Both procedural and fluoroscopy times, as well as

anterior descending artery CTO) experienced cardiac

air kerma radiation exposure were similar in the 3

death (33.3%) due to refractory heart failure, 2 and 5

groups; whereas, less contrast load was used in pa-

months after the failed CTO PCI. MACCE occurred less

tients with LVEF #35% in comparison with group 1

frequently in patients with successful CTO PCI (16.6%

and group 2 (295.6
159 ml vs. 369.9
213.9 ml vs.

vs. 50.0%; p ¼ 0.083) and were especially driven by

349.1
197.7 ml; p ¼ 0.005 and p ¼ 0.038, respec-

non-CTO TVR (n ¼ 6 [9.1%]) (Table 5).

tively). Procedural details are summarized in Table 3.

At midterm follow-up, in case of successful CTO

In patients with LVEF #35%, viability in the terri-

PCI, no difference in MACCE occurrence was observed

tory

subtended

by

the

CTO

was

assessed

by

in the 3 groups (10.2% vs. 13.9% vs. 16.6%; all p ¼ NS),

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CTO PCI and Low LVEF

whereas in case of failed CTO PCI cardiac death was more

frequently

observed

in

patients

with

LVEF #35% in comparison with those with mildly

F I G U R E 3 Severity of Coronary Artery Disease Lesions in

Patients with LVEF #35%

impaired and preserved LVEF (33.3% vs. 8.3% mildly impaired LVEF, p ¼ 0.001; and vs. preserved LVEF 3%, p < 0.001 (Table 5). At 2 years, MACCE-free survival was similar in the 3 groups (86% vs. 82.8% vs. 75.2%; all p ¼ NS) (Figure 4). Of note, health care center did not affect the midterm clinical outcome (hazard ratio [HR]: 1.07; 95% CI: 0.93 to 1.23; p ¼ 0.821). On multivariate Cox regression, independent predictors of MACCE at midterm follow-up were as follows: age (per decade) (HR: 1.40; 95% CI: 1.07 to 1.98; p ¼ 0.037), diabetes mellitus (HR: 2.71; 95% CI: 1.17 to 4.90; p ¼ 0.017), and CTO PCI failure (HR: 3.45; 95% CI: 1.74 to 6.32; p < 0.001]; LVEF #35% did not predict MACCE occurrence (HR: 1.52; 95% CI: 0.66 to 2.92; p ¼ 0.398) (Figure 5). Regarding symptoms, a significant improvement of dyspnea

was

only

observed

in

patients

with

LVEF #35%, whereas an improvement of angina occurred in patients with preserved LVEF (Figure 6). In patients with LVEF #35%, the use of percutaneous mechanical circulatory support (HR: 1.10; 95% CI: 0.13 to 8.96; p ¼ 0.929) and the achievement of SRI $70% (HR: 1.17; 95% CI: 0.28 to 4.94; p ¼ 0.829) did not influence MACCE occurrence. In patients with LVEF #35% who underwent successful CTO PCI, LVEF improved significantly at 6 months (from 29.1
3.4% to 41.6
7.9%; p < 0.001) (Figure 7). Angiographic control was performed in 49 (74.2%) patients (4 driven

(A) Number of diseased coronary artery vessels according to CTO target vessel. (B) baseline SYNTAX score (bSS) and re-

by ischemia and 45 systematically) after a mean period

sidual SYNTAX score (rSS) in successful and failed CTO PCI at-

of 8.7
2.3 months, whereas the remaining 14 alive

tempts. LAD ¼ left anterior descending artery; LCX ¼ left

patients had improved symptoms and refused angio-

circumflex artery; RCA ¼ right coronary artery; other abbre-

graphic control. Focal nonocclusive restenosis of CTO

viations as in Figure 1.

target vessel was found in 4 cases (8.2%), requiring further revascularization, whereas neither diffuse restenosis nor reocclusion was observed. Severe ischemic left ventricular dysfunction is

DISCUSSION

associated with higher morbidity, an increased risk of sudden death due to ventricular arrhythmias, poor

The most important findings of our study can be

quality of life, and frequent re-hospitalization for

summarized as follows: 1) PCI represents an efficient

heart failure. In the COMMIT-HF (ConteMporary

as well as safe strategy in patients with low LVEF

Modalities In Treatment of Heart Failure) registry

(#35%) affected by CTOs; 2) successful CTO PCI in

including 675 patients with ischemic systolic heart

these

significant

failure (LVEF #35%) who underwent elective coro-

improvement of LVEF and symptoms, in particular

nary angiography, a CTO was present in 278 patients,

patients

was

associated

with

dyspnea, at 6-month follow-up; 3) successful CTO PCI

accounting for an overall prevalence of 41.2% (11).

improved the midterm clinical outcome in patients

The patients with CTO had a higher frequency of

with LVEF #35% as well in those with mildly

previous MI, higher prevalence of diabetes, and

impaired and preserved LVEF; and 4) low LVEF did

higher percentage of multivessel coronary artery

not represent an independent predictor of MACCE at

disease (11). Our data confirmed that CTO patients

follow-up.

with low LVEF had higher risk profile with more

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T A B L E 4 Periprocedural Complications

All CTO PCI (N ¼ 839)

LVEF $50% CTO PCI (n ¼ 552) (Group 1)

LVEF 35%–50% CTO PCI (n ¼ 215) (Group 2)

LVEF #35% CTO PCI (n ¼ 72) (Group 3)

Coronary perforation without tamponade

21 (2.5)

17 (4.5)

6 (2.8)

3 (4.2)

Coronary perforation with tamponade

13 (1.5)

8 (1.4)

5 (2.3)

0

Need for emergency CABG

1 (0.1)

1 (0.2)

0

0

0

0

0

0 0

Death Non–Q-wave MI

7 (0.8)

3 (0.5)

4 (1.9)

Q-wave MI

2 (0.2)

2 (0.4)

0

0

Stent thrombosis

2 (0.2)

1 (0.2)

1 (0.5)

0

TVR

4 (0.5)

2 (0.4)

2 (0.9)

0

0

0

0

0

3 (0.4)

2 (0.4)

1 (0.5)

0

Stroke Major bleeding Values are n (%).

TVR ¼ target vessel revascularization; other abbreviations as in Table 1.

comorbidities and more diffuse CAD in comparison

Interestingly,

with those with preserved and mildly impaired LVEF.

LVEF #35% included in our study population were

CTO

lesions

in

patients

with

Tajstra et al. (11) also found that in patients with

less previously attempted than in those with pre-

systolic heart failure, 12-month all-cause mortality

served and mildly impaired LVEF. This fact might

(19.4% vs. 13.1%; p < 0.001) and cardiovascular death

underline the reluctance of non-CTO expert inter-

(16.2% vs. 8.3%; p ¼ 0.001) were higher in presence of

ventionalists to attempt such more difficult proced-

CTO than without. The presence of CTO indepen-

ures in this high-risk subset of patients, preferring to

dently increased the risk of 12-month mortality

refer them to CTO expert operators or to open heart

(relative risk: 1.84; 95% CI: 1.18 to 2.85; p ¼ 0.006).

surgery.

Importantly, in the latter study, only a minority of

In our study, the angiographic success rate of CTO

patients was affected by CTOs attempted percutane-

PCI attempts was 93.6% in all population and 91.7% in

ously (3.5%) (11). Current guidelines and appropriate

patients with LVEF was #35%. Moreover, low LVEF

use criteria for myocardial revascularization do not

did not predict CTO PCI failure. Although the CTO

provide any recommendation regarding the most

recanalization techniques used in this latter subset of

appropriate management strategy in CTO patients

patients were comparable to those used in patients

with low LVEF (20,21).

with preserved and mildly impaired LVEF, some

Thanks to the development of dedicated equip-

particularities should be emphasized. For instance, in

ment and the growing expertise of CTO PCI operators,

patients with a dilated left ventricle (left ventricular

the success rate has dramatically increased among

end-diastolic diameter $70 mm), the retrograde

different interventionalists’ communities (9,22,23). In

approach requires longer microcatheters and in some

addition, despite the increasing complexity of CTO

cases brachial access with shortened guiding cathe-

lesions,

ters (80 cm) to facilitate externalization. In addition,

complication

rates

remained

low

(9).

T A B L E 5 Clinical Follow-Up of CTO Patients According to LVEF

LVEF $50% Group 1 (n ¼ 509)

Successful CTO PCI (n ¼ 476)

All-cause death

8 (1.6)

5 (1.1)

Cardiac death

4 (0.8)

3 (0.6)

LVEF #35%

LVEF 35%–50%

Failed CTO PCI (n ¼ 33)

p Value

Group 2 (n ¼ 200)

Successful CTO PCI (n ¼ 188)

3 (9.1)

0.011

4 (2.0)

3 (1.6)

1 (3.0)

0.236

3 (1.5)

2 (1.1)

Failed CTO PCI (n ¼ 12)

p Value

Group 3 (n ¼ 72)

Successful CTO PCI (n ¼ 66)

Failed CTO PCI (n ¼ 6)

1 (8.3)

0.221

1 (8.3)

0.170

p Value

6 (8.3)

3 (4.5)

3 (50.0)*†

0.006

3 (4.2)

1 (1.5)

2 (33.3)†

0.017

Nonfatal MI

20 (3.9)

17 (3.6)

3 (12.1)

0.133

8 (4.0)

7 (3.7)

1 (8.3)

0.396

2 (2.8)

2 (3.0)

0

0.839

TVR

18 (3.5)

18 (3.8)

0

0.293

6 (3.0)

6 (3.2)

0

0.687

4 (5.6)

4 (6.1)

0

0.701

Non-TVR

20 (3.9)

17 (3.6)

3 (9.1)

0.133

17 (8.5)

15 (8.0)

2 (16.6)

0.271

7 (9.7)

6 (9.1)

1 (16.7)

0.471

Stroke

5 (9.8)

4 (0.8)

1 (3.0)

0.286

0

0

0

—

1 (1.4)

0

1 (16.7)

0.083

MACCE

59 (11.6)

51 (10.2)

8 (24.2)

0.027

30 (15.0)

26 (13.9)

4 (33.3)

0.086

14 (19.4)†

11 (16.6)

3 (50.0)

0.083

Values are n (%). *Group 1 vs. group 3, p < 0.05. †Group 2 vs. group 3, p < 0.05. MACCE ¼ major adverse cardiac and cerebrovascular event(s); TVR ¼ target vessel revascularization; other abbreviations as in Table 1.

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F I G U R E 4 Long-Term Clinical Outcome According to LVEF

(A) Kaplan-Meier curves in patients who underwent CTO PCI attempts. (B) Kaplan-Meier curves in patients who underwent successful CTO revascularization. (C) Kaplan-Meier curves in patients with failed CTO PCI attempts. MACCE ¼ major adverse cardiac and cerebrovascular event(s); other abbreviations as in Figure 1.

the use of pMCS, albeit not associated with improved

revascularization as a valuable option in this subset of

midterm

while

patients (28). In this respect, Généreux et al. (29)

attempting CTO in such high-risk patients, particu-

considered an SRI $70% representing a “reasonable”

larly due to the danger of hemodynamic collapse in a

goal for patients with complex coronary artery disease.

outcome,

could

be

of

benefit

severe depressed LVEF (24). Special attention should

Several observational studies and meta-analyses

also be paid to the amount of contrast used, as these

showed that successful CTO PCI was associated with

patients are at high-risk of contrast-induced nephropathy. Indeed, Liu et al. (25) developed a preprocedural risk score to predict contrast induced ne-

F I G U R E 5 Predictors of MACCE Occurrence at Follow-Up

phropathy after CTO PCI based on 3 variables, and including LVEF #40%. Similar to other recent reports (9,26), a low rate of periprocedural complications was observed in our study. Importantly, except 3 cases of type I perforations (Ellis classification), no patients with low LVEF experienced severe periprocedural complications after CTO PCI. Hence, our data suggest that in experienced hands, CTO PCI represents a safe strategy even in high-risk patients, able to achieve a high degree of revascularization, as witnessed by the achievement of SRI $70% in almost three-quarters of patients. In patients with multivessel coronary artery disease, incomplete revascularization has been recognized to be associated with increased risk of death or cardiac adverse events, proportionally to the level of incompleteness of the revascularization (27). Nonetheless, a body of evidence is emerging and suggesting that complete revascularization could not be the only overriding tenet. Indeed, especially in high-risk patients, reduction of the procedural risk may be a preferred strategy, and a groundswell of published data supports the concept of reasonable incomplete

The independent predictors of MACCE at follow-up were the following: age (decade), diabetes, and failed CTO PCI. CI ¼ confidence interval; CKD ¼ chronic kidney disease; other abbreviations as in Figures 1 and 5.

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CTO PCI and Low LVEF

F I G U R E 6 Changes in Symptoms 6 Months After CTO PCI According to LVEF

(A) Changes in angina 6 months after CTO PCI according to LVEF. (B) Changes in dyspnea 6 months after CTO PCI according to LVEF. CCS ¼ Canadian Cardiovascular Society; NYHA ¼ New York Heart Association; other abbreviations as in Figure 1.

improved cardiovascular prognosis in comparison

follow-up. Indeed, in patients with LVEF #35% who

with unsuccessful procedures (30–33). In the current

underwent successful CTO recanalization: only 1

study, a good clinical midterm outcome was achieved

cardiac death (1.5%) occurred and the majority of

in the 3 groups and low LVEF was not demonstrated

MACCE

to be an independent predictor of MACCE at midterm

LVEF #35% did not predict the occurrence of MACCE,

were

due

to

non-CTO

TVR.

Although

in case of failed CTO PCI more patients experienced cardiac death in low LVEF group than in presence of F I G U R E 7 Improvement of LVEF After Successful of CTO PCI

in Patients With Low LVEF #35%

mildly impaired or preserved LVEF (Table 5), underlying the need not only for expertise to treat CTOs but also for appropriate models to predict success in such a subset of patients to achieve better outcome. Hoebers et al. (31) performed a weighted metaanalysis of 34 studies (including 2,243 patients) addressing the change of LVEF after successful CTO PCI. After a follow-up period ranging from 1 to 36 months, LVEF increased significantly with a pooled estimate of 4.44% (p < 0.01). Although it is common to consider a difference of at least 5% in LVEF as clinically significant, the impact of CTO revascularization on LVEF was relatively underestimated in the

In CTO patients with low LVEF, successful CTO PCI resulted in LVEF improvement from 29.1
3.4% to 41.6
7.9%

latter meta-analysis because of the heterogeneity (I 2 ¼ 44%) between studies due to the difference in

(þ42.9%; p < 0.001) at 6-month follow-up. Abbreviations

cohort sizes, CTO definition, CTO location, success

as in Figure 1.

definition, imaging modality, and follow-up duration (33). However, in the case of reocclusion of the target

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CTO PCI and Low LVEF

CTO vessel, LVEF was similar and even relatively

dyspnea in patients with low LVEF and less angina in

worse than that at baseline (–0.15%). This latter fact

those with preserved LVEF. The results of the ran-

might be explained by the loss of the protective ef-

domized EURO-CTO (Randomized Multicenter Trial

fect of collaterals after initial restoration of ante-

to Evaluate the Utilization of Revascularization or

grade flow (32). Additionally, 8 studies reported

Optimal Medical Therapy for the Treatment of

significant decreases in left ventricle end-diastolic

Chronic Total Occlusions) trial (NCT01760083) are

volume (6.14 ml/m 2; 95% CI: –9.31 to –2.97; p < 0.01)

expected to better evaluate the impact of PCI on the

(32). In our study, a significant improvement of

quality-of-life parameters in patients affected by CTO

LVEF (þ42.9%; p < 0.001) was obtained 6 months

when compared with optimal medical therapy alone.

after

successful

with

Finally, needless to say that improvement of sur-

LVEF #35%. Similarly, in a cardiac magnetic reso-

vival and symptoms in patients with left ventricular

nance

study

CTO

PCI

including

29

in

patients

with

dysfunction undergoing myocardial revascularization

LVEF #40%, Cardona et al. (34) showed that success-

CTO

patients

(of either CTO or non-CTO lesions) is only obtained

ful CTO PCI resulted in a significant increase in

when viability is demonstrated (38).

LVEF (from 31.3
7.4% to 37.7
8.0%; p < 0.001) and a significant decrease in left ventricular end-

STUDY LIMITATIONS. First,

systolic volume (from 160
54 ml to 143
58 ml;

patients with LVEF #35% was relatively small;

p ¼ 0.029). Hence, percutaneous revascularization

however, it reflects a real-world multicenter experi-

of CTOs subtending viable myocardial territory of

ence, and patients with low LVEF currently account

hemodynamic importance, in the setting of systolic

for a minority of CTO patients referred for PCI.

dysfunction leads to improved LVEF and reduced

Second, all procedures were performed by CTO

adverse remodeling resulting in positive clinical con-

expert operators; hence, the present results may not

sequences, particularly in absence of reocclusion.

be applicable to the entire population of inter-

In the recent EXPLORE (Evaluating Xience and Left Ventricular Intervention Myocardial

Function on

in

Percutaneous

Occlusions

Infarction)

trial,

After 150

the number of CTO

ventionalists. Third, the definition used for non–Q-

Coronary

wave MI could underestimate its occurrence. Fourth,

ST-Elevation

the LVEF was assessed by 2-dimensional echocardi-

patients

were

ography in the different centers involved, and no core

randomly assigned to early PCI of the CTO and 154

lab analysis was performed. Fifth, bSS and rSS were

patients were assigned to conservative treatment

only calculated in patients with LVEF #35%. Sixth,

without PCI of the CTO (35). At 4-month follow-up,

53 patients were lost at follow-up; nonetheless,

mean LVEF did not differ between the 2 groups.

complete data were available in 93.1% of our initial

Nonetheless, this finding was likely due to a more

cohort. Seventh, angiographic control was only

substantial impact of the infarct-related artery than

performed in 74.2% of low LVEF CTO patients suc-

the CTO itself on left ventricle dysfunction. Interest-

cessfully revascularized, whereas no angiographic

ingly, subgroup analysis revealed that patients with

follow-up data were collected in other LVEF groups.

CTO located in the left anterior descending coronary

Eighth, no adjustment was made for multiple statis-

artery who were randomized to the CTO PCI strategy

tical comparisons. Finally, our study did not compare

had significantly higher LVEF compared with patients

the results of PCI versus CABG in patients with

randomized to the no CTO PCI strategy (47.2
12.3%

low LVEF.

vs. 40.4
11.9%; p ¼ 0.02) (35). On the other hand, several observational studies

CONCLUSIONS

showed that successful CTO revascularization is associated with improved quality of life (36,37). The

Patients with ischemic left ventricular dysfunction

European CTO club has reported the long-term

(LVEF #35%), particularly those affected by CTOs,

outcome of 5-year retrograde experience showing a

belong to a high-risk subset of patients, in whom the

significant improvement in both angina and dyspnea

appropriate management strategy is not well estab-

status after a median follow-up period of 23 months

lished yet. Our results showed that in experienced

(9). Symptomatic patients with CTO particularly tend

hands, PCI could represent a safe and efficient man-

to adapt to their condition, and will frequently avoid

agement strategy able to improve LVEF and symp-

symptom-generating physical activity. In addition,

toms, and to ensure good midterm outcome.

many of them (not only those with low LVEF) will experience dyspnea more than from angina on exer-

ADDRESS FOR CORRESPONDENCE: Dr. Alfredo R.

tion

Galassi, Via Antonello da Messina 75, Acicastello,

(19).

Our

results

confirmed

a

significant

improvement in symptoms after CTO PCI: less

95021 Catania, Italy. E-mail: [email protected].

11

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CTO PCI and Low LVEF

PERSPECTIVES WHAT IS KNOWN? In patients with ischemic left

able to improve LVEF and symptoms and ensure good

ventricular dysfunction, the presence of CTO is

midterm outcome.

associated with reduced survival and worse WHAT IS NEXT? Further studies are required to

cardiovascular outcome.

confirm these preliminary data regarding the WHAT IS NEW? PCI represents a safe and efficient

outcomes of CTO PCI in such a high-risk subset of

management strategy in CTO patients with low LVEF,

patients.

REFERENCES 1. Tomasello SD, Boukhris M, Giubilato S, et al. Management strategies in patients affected by chronic total occlusions: results from the Italian Registry of Chronic Total Occlusions. Eur Heart J 2015;36:3189–98. 2. Råmunddal T, Hoebers LP, Henriques JP, et al. Chronic total occlusions in Sweden—a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). PLoS One 2014;12: e103850. 3. Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. J Am Coll Cardiol 2012;59: 991–7. 4. Jeroudi OM, Alomar ME, Michael TT, et al. Prevalence and management of coronary chronic total occlusions in a tertiary veterans affairs hospital. Catheter Cardiovasc Interv 2014;84:637–43. 5. Gierlotka M, Tajstra M, Ga ˛sior M, et al. Impact of chronic total occlusion artery on 12-month mortality in patients with non–ST-segment elevation myocardial infarction treated by percutaneous coronary intervention (from the PL-ACS Registry). Int J Cardiol 2013;168:250–4. 6. van der Schaaf RJ, Vis MM, Sjauw KD, et al. Impact of multivessel coronary disease on longterm mortality in patients with ST-elevation myocardial infarction is due to the presence of a chronic total occlusion. Am J Cardiol 2006;98: 1165–9. 7. Farooq V, Serruys PW, Garcia-Garcia HM, et al. The negative impact of incomplete angiographic revascularization on clinical outcomes and its association with total occlusions: the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial. J Am Coll Cardiol 2013;61:282–94. 8. Galassi AR, Boukhris M, Azzarelli S, Castaing M, Marzà F, Tomasello SD. Percutaneous coronary revascularization for chronic total occlusions: a novel predictive score of technical failure using advanced technologies. J Am Coll Cardiol Intv 2016;9:911–22. 9. Galassi AR, Sianos G, Werner GS, et al. 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;65:2388–400.

10. Emond M, Mock MB, Davis KB, et al. Longterm survival of medically treated patients in the Coronary Artery Surgery Study (CASS) registry. Circulation 1994;90:2645–57. 11. Tajstra M, Pyka Ł, Gorol J, et al. Impact of chronic total occlusion of the coronary artery on long-term prognosis in patients with ischemic systolic heart failure: insights from the COMMITHF registry. J Am Coll Cardiol Intv 2016;9:1790–7. 12. Sianos G, Werner GS, Galassi AR, et al. Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention 2012;8:139–45. 13. Morino Y, Abe M, Morimoto T, et al. 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. J Am Coll Cardiol Intv 2011;4: 213–21. 14. Ellis SG, Ajluni S, Arnold AZ, et al. Increased coronary perforation in the new device era. Incidence, classification, management, and outcome. Circulation 1994;90:2725–30. 15. Amlani SNT, Afzal R, Pal-Sayal R, Eikelboom JW, Natarajan MK. Mortality and morbidity following a major bleed in a registry population with acute ST elevation myocardial infarction. J Thromb Thrombolysis 2010;30: 434–40. 16. Kobayashi Y, Nam CW, Tonino PA, et al. The prognostic value of residual coronary stenoses after functionally complete revascularization. J Am Coll Cardiol 2016;67:1701–11. 17. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003. 18. McMurray JJ, Adamopoulos S, Anker SD, et al. The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:803–69. 19. Galassi AR, Brilakis ES, Boukhris M, et al. Appropriateness of percutaneous revascularization

of coronary chronic total occlusions: an overview. Eur Heart J 2016;37:2692–700. 20. Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg 2014;46: 517–92. 21. Patel MR, Dehmer GJ, Hirshfeld JW, Smith PK, Spertus JA. ACCF/SCAI/STS/AATS/AHA/ASNC/ HFSA/SCCT 2012 Appropriate use criteria for coronary revascularization focused update: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, American Society of Nuclear Cardiology, and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2012;59:857–81. 22. Inohara T, Kohsaka S, Miyata H, et al. Realworld use and appropriateness of coronary interventions for chronic total occlusion (from a Japanese multicenter registry). Am J Cardiol 2015; 116:858–64. 23. Karatasakis A, Tarar MN, Karmpaliotis D, et al. Guidewire and microcatheter utilization patterns during antegrade wire escalation in chronic total occlusion percutaneous coronary intervention: Insights from a contemporary multicenter registry. Catheter Cardiovasc Interv 2016 [ahead of print]. 24. Tomasello SD, Boukhris M, Ganyukov V, et al. Outcome of extracorporeal membrane oxygenation support for complex high-risk elective percutaneous coronary interventions: A singlecenter experience. Heart Lung 2015;44:309–13. 25. Liu Y, Liu YH, Chen JY, et al. A simple pre-procedural risk score for contrast-induced nephropathy among patients with chronic total occlusion undergoing percutaneous coronary intervention. Int J Cardiol 2015;180:69–71. 26. Danek BA, Karatasakis A, Karmpaliotis D, et al. Development and validation of a scoring system for predicting periprocedural complications during

JACC: CARDIOVASCULAR INTERVENTIONS VOL.

-, NO. -, 2017

- 2017:-–-

percutaneous coronary interventions of chronic total occlusions: the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) complications score. J Am Heart Assoc 2016;5:e004272. 27. Milojevic M, Head SJ, Parasca CA, et al. Causes of death following PCI versus CABG in complex CAD: 5-year follow up of SYNTAX. J Am Coll Cardiol 2016;67:42–55. 28. Dauerman HL. Reasonable incomplete revascularization. Circulation 2011;123:2337–40. 29. Généreux P, Campos CM, Yadav M, et al. Reasonable incomplete revascularisation after percutaneous coronary intervention: the SYNTAX Revascularisation Index. EuroIntervention 2015;11:634–42. 30. Joyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. Am Heart J 2010;160:179–87. 31. Hoebers LP, Claessen BE, Elias J, Dangas GD, Mehran R, Henriques JP. Meta-analysis on the impact of percutaneous coronary intervention of

Galassi et al. CTO PCI and Low LVEF

chronic total occlusions on left ventricular function and clinical outcome. Int J Cardiol 2015;187:90–6. 32. George S, Cockburn J, Clayton TC, et al. Longterm follow-up of elective chronic total coronary occlusion angioplasty: analysis from the U.K. Central Cardiac Audit Database. J Am Coll Cardiol 2014;64:235–43. 33. Boukhris M, Elhadj ZI, Galassi AR. Chronic total improvement in ventricular function and survival. J Thorac Dis 2015;7:E222–5. 34. Cardona M, Martín V, Prat-Gonzalez S, et al. Benefits of chronic total coronary occlusion percutaneous intervention in patients with heart failure and reduced ejection fraction: insights from a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 2016;

36. Safley DM, Grantham JA, Hatch J, Jones PG, Spertus JA. Quality of life benefits of percutaneous coronary intervention for chronic occlusions. Catheter Cardiovasc Interv 2014;84:629–34. 37. Wijeysundera HC, Norris C, Fefer P, et al. Relationship between initial treatment strategy and quality of life in patients with coronary chronic total occlusions. EuroIntervention 2014;9:1165–72. 38. Gerber BL, Rousseau MF, Ahn SA, et al. Prognostic value of myocardial viability by delayed-enhanced magnetic resonance in patients with coronary artery disease and low ejection fraction: impact of revascularization therapy. J Am Coll Cardiol 2012;59:825–35.

18:78.

KEY WORDS chronic total occlusion,

35. Henriques JP, Hoebers LP, Råmunddal T, et al.

ischemic LV dysfunction, left ventricular ejection fraction, PCI

Percutaneous Intervention for Concurrent Chronic Total Occlusions in Patients With STEMI: The EXPLORE Trial. J Am Coll Cardiol 2016;68: 1622–32.

A PP END IX For a supplemental figure, please see the online version of this article.

13