Impact of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention on Long-Term Clinical Outcomes in Patients Undergoing Complex Procedures

JACC: CARDIOVASCULAR INTERVENTIONS

VOL.

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ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

Impact of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention on Long-Term Clinical Outcomes in Patients Undergoing Complex Procedures Ki Hong Choi, MD,a Young Bin Song, MD, PHD,a Joo Myung Lee, MD, MPH, PHD,a Sang Yoon Lee, MD,a Taek Kyu Park, MD, PHD,a Jeong Hoon Yang, MD, PHD,a,b Jin-Ho Choi, MD, PHD,a,c Seung-Hyuk Choi, MD, PHD,a Hyeon-Cheol Gwon, MD, PHD,a Joo-Yong Hahn, MD, PHDa

ABSTRACT OBJECTIVES This study sought to determine whether intravascular ultrasound (IVUS) guidance compared with angiographic guidance reduces long-term risk of cardiac death in patients undergoing complex percutaneous coronary intervention (PCI). BACKGROUND Although IVUS is a useful tool for accurate assessment of lesion profiles and optimal stent implantation, there are limited data on long-term clinical outcomes between IVUS-guided and angiography-guided PCI for patients with complex lesions. METHODS From March 2003 through December 2015, a total of 6,005 patients undergoing PCI for complex lesions with drug-eluting stents were enrolled from a prospective institutional registry. All enrolled subjects had at least 1 complex lesion (defined as bifurcation, chronic total occlusion, left main disease, long lesion, multivessel PCI, multiple stent implantation, in-stent restenosis, or heavily calcified lesion). Patients were classified according to use of IVUS or not. Multiple sensitivity analyses, including multivariable adjustment, propensity-score matching, and inverse-probability-weighted method, were performed to adjust baseline differences. RESULTS Among the study population, IVUS was used in 1,674 patients (27.9%) during complex PCI. The IVUS-guided PCI group had a significantly larger mean stent diameter (3.2
0.4 vs. 3.0
0.4; p < 0.001), and more frequent use of post-dilatation (49.0% vs. 17.9%; p < 0.001) compared with the angiography-guided PCI group. IVUS-guided PCI was associated with a significantly lower risk of cardiac death during 64 months of median follow-up compared with angiography-guided PCI (10.2% vs. 16.9%; hazard ratio: 0.573; 95% confidence interval: 0.460 to 0.714; p < 0.001). Results were consistent after multivariable regression, propensity-score matching, and inverse-probability-weighted method. The risks of all-cause death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, and major adverse cardiac events were also significantly lower in the IVUS-guided PCI group. CONCLUSIONS Among patients with complex coronary artery lesion, IVUS-guided PCI was associated with the lower long-term risk of cardiac death and adverse cardiac events compared with angiography-guided PCI. Use of IVUS should be actively considered for complex PCI. (J Am Coll Cardiol Intv 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

From the aDivision of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; bDepartment of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; and the cDepartment of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received November 26, 2018; revised manuscript received January 2, 2019, accepted January 15, 2019.

ISSN 1936-8798/$36.00

https://doi.org/10.1016/j.jcin.2019.01.227

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IVUS-Guided PCI for Complex Coronary Lesion

ince the introduction of the second-

long lesion (implanted stent length $38 mm); 5)

generation drug-eluting stent (DES),

multivessel PCI ($2 major epicardial coronary vessels

the rates of device-related failure or

treated at 1 PCI session); 6) multiple stent implanta-

target lesion failure, such as restenosis

tion (3 or more stents per patient); 7) in-stent reste-

and stent thrombosis (ST), have markedly

nosis lesion; or 8) severely calcified lesion (requiring

decreased compared with the era of the

a rotablator system). For the purpose of the present

HR = hazard ratio

bare-metal stent or first-generation DES

study, enrolled patients were divided into those un-

IPW = inverse-probability-

(1,2).

ABBREVIATIONS AND ACRONYMS CI = confidence interval CTO = chronic total occlusion DES = drug-eluting stent(s)

weighted

Nevertheless,

patients

undergoing

percutaneous coronary intervention (PCI)

IVUS = intravascular

for complex lesions including chronic total

ultrasound

MI = myocardial infarction PCI = percutaneous coronary intervention

ST = stent thrombosis TLR = target lesion revascularization

dergoing IVUS-guided PCI (n ¼ 1,674) and those undergoing angiography-guided PCI (n ¼ 4,331). Baseline characteristics, angiographic and proce-

occlusion (CTO), left main disease, true bifur-

dural

cation lesion, long lesion, multivessel PCI,

prospectively in our PCI registry by research co-

multiple overlapping stents, in-stent reste-

ordinators. Additional information was obtained from

nosis, or severely calcified lesions have

medical records and telephone interviews, if neces-

significantly worse clinical outcomes than

sary. The mortality data for patients who were lost to

those with noncomplex lesions (3–5).

follow-up were confirmed by National Death Records.

data,

and

outcome

data

were

collected

Intravascular ultrasound (IVUS) is a useful

The study protocol was approved and the require-

tool during the PCI procedure for providing informa-

ment for informed consent of the individual patients

tion

characteristics,

was waived by the Institutional Review Board

including vulnerable plaques, lesion severity, length,

of Samsung Medical Center, and this study was

and morphology; on post-intervention optimal stent

conducted according to the principles of the Decla-

implantation for stent expansion, extension, and

ration of Helsinki.

on

pre-intervention

lesion

apposition; and on possible complications after stent implantation (6–8). Although previous randomized controlled trials and registries showed significantly lower rates of adverse clinical events following IVUSguided PCI compared with angiography-guided PCI, they were limited by small sample size or relatively short-term follow-up duration (9–11). Furthermore, since the previous studies focused on specific subsets of lesions (12–16), there have been limited data regarding the long-term outcomes of IVUS-guided PCI for patients with various complex coronary lesions, who are expected to benefit the most from use of IVUS in clinical practice (17). Therefore, we compared the long-term clinical outcomes of IVUS-guided PCI with angiography-guided PCI in an all-comer study of complex coronary artery lesions.

METHODS PATIENT POPULATION AND DATA COLLECTION.

This was a retrospective, single-center, observational study. Between May 2003 and December 2015, a total of 6,005 consecutive patients who had a complex

PCI AND IVUS. The PCI procedure and best available

medical therapy were performed according to the standard procedural guidelines (18,19). All patients received a loading dose of aspirin (300 mg) and P2Y 12 inhibitors (clopidogrel 300 to 600 mg, ticagrelor 180 mg, or prasugrel 60 mg) before coronary intervention unless they had previously received these antiplatelet medications. The revascularization treatment strategy,

use

of

glycoprotein

IIb/IIIa

receptor

inhibitors, choice of DES, duration of dual antiplatelet therapy, or any adjunctive pharmacologic treatment after PCI were left to the operator’s preference. In the IVUS-guided PCI group, timing of IVUS (before stenting, after DES implantation, or both) was also left to the operator’s discretion. All IVUS images were obtained after administration of intracoronary nitroglycerin (200 mg) using a commercially available system (Boston Scientific Corporation, San Jose, California; or Volcano Corporation, Rancho Cordova, California). The transducer was pulled back automatically at a speed of 0.5 mm/s, whenever possible.

coronary artery lesion and underwent PCI with

DEFINITIONS

DES were enrolled from a prospective institutional

outcome of this study was cardiac death during

AND

OUTCOMES. The

cardiovascular catheterization database of Samsung

follow-up. Secondary outcomes included all-cause

Medical Center, Seoul, Republic of Korea. The

death; myocardial infarction (MI); definite or prob-

detailed study flow diagram is depicted in Figure 1.

able ST; ischemia-driven target lesion revasculariza-

Complex lesions were defined as 1 of the following: 1)

tion (TLR); and major adverse cardiac events, which

bifurcation lesions with side branch diameter $2.5

comprised a composite of cardiac death, MI, ST, and

mm; 2) CTOs with an occlusion duration $3 months;

ischemia-driven TLR. All deaths were considered to

3) unprotected left main coronary artery disease; 4)

be cardiac unless a definite noncardiac cause was

primary

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IVUS-Guided PCI for Complex Coronary Lesion

F I G U R E 1 Study Flow

*MACE was defined as a composite of cardiac death, myocardial infarction, stent thrombosis, and ischemia-driven target lesion revascularization. DES ¼ drug-eluting stent(s); MACE ¼ major adverse cardiac event(s); PCI ¼ percutaneous coronary intervention.

documented. MI was defined as an elevation of cre-

stenosis with final Thrombolysis In Myocardial

atine kinase–myocardial band or troponin level

Infarction flow grade 3.

greater than the upper limit of normal with concomitant ischemic symptoms or electrocardiography

STATISTICAL ANALYSIS. Continuous variables were

findings indicative of ischemia (20). Periprocedural

compared using Welch t test, and categorical vari-

MI was not included as clinical event. Definite or

ables were compared using chi-square test. The cu-

probable ST was defined using the definitions of the

mulative incidence of clinical events was evaluated

Academic Research Consortium (21). Ischemia-driven

by Kaplan-Meier analyses and significance level was

TLR was defined as a revascularization procedure at

assessed with the log-rank test. The hazard ratio (HR)

the previously treated segment from 5 mm proximal

and 95% confidence intervals (CIs) were calculated by

to the stent to 5 mm distal to the stent with $50%

a Cox proportional hazards model to compare

diameter stenosis and at least 1 of the following: 1)

the outcomes between the IVUS-guided PCI and

recurrence of angina; 2) positive noninvasive test; or

angiography-guided PCI groups. Multiple sensitivity

3) positive invasive physiologic test. All events were

analyses including multivariable Cox proportional

adjudicated by an expert of interventional cardiology

hazards

in a blinded fashion of treatment strategy. Angio-

(IPW), and propensity-score matched analyses were

graphic success of PCI was defined as #30% residual

performed to adjust for baseline differences.

regression,

inverse-probability-weighted

3

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IVUS-Guided PCI for Complex Coronary Lesion

T A B L E 1 Baseline Clinical Characteristics in Patients With Complex Coronary Artery

Lesions Undergoing PCI According to Use of Intravascular Ultrasound

after propensity-score matching or IPW adjustment were within
10% across all matched covariates, suggesting successful balance achievement between

Intravascular Ultrasound–Guided (n ¼ 1,674)

Angiography-Guided (n ¼ 4,331)

p Value

62.0
10.5 1,316 (78.6) 24.6
2.9

63.8
11.0 3,202 (73.9) 24.6
3.1

<0.001 <0.001 0.665

959 (57.3) 689 (41.2) 113 (6.8) 524 (31.3) 324 (19.4) 322 (19.2) 249 (14.9) 80 (4.8) 40 (2.4)

2,669 (61.6) 2,161 (49.9) 431 (10.0) 1,360 (31.4) 930 (21.5) 954 (22.0) 796 (18.4) 309 (7.1) 112 (2.6)

0.002 <0.001 <0.001 0.965 0.076 0.019 0.002 0.001 0.732

the 2 groups (Online Table 2). Stratified and IPWadjusted Cox proportional hazards models were used to compare the outcomes of the matched

Demographics Age, yrs Male Body mass index, kg/m2 Cardiovascular risk factors Hypertension Diabetes mellitus Chronic kidney disease Hyperlipidemia Current smoker Previous PCI Previous MI Previous cerebrovascular accident Peripheral artery disease

groups. Finally, a landmark analysis using the timedependent

coefficient

Cox

proportional

hazards

models assessed the hazard before and after the change point of 365 days and compared the outcomes between the 2 groups, carefully verifying the proportional hazard assumptions of the model. A likelihood ratio test was performed to evaluate the value of the change point analysis rather than the constant hazard Cox model. All

probability

values

were

2-sided,

and

p

values <0.05 were considered statistically significant.

Initial presentation Clinical presentation Stable angina Unstable angina Non-ST-segment elevation MI ST-segment elevation MI Silent ischemia LVEF, %

946 (56.5) 390 (23.3) 117 (7.0) 61 (3.6) 160 (9.6) 60.1
10.7

2,124 (49.0) 801 (18.5) 447 (10.3) 509 (11.8) 450 (10.4) 57.5
12.5

<0.001

Medications at the index procedure Aspirin P2Y12 inhibitors Statin Beta-blocker ACE inhibitor or ARB

1,567 (93.6) 1,586 (94.7) 1,510 (90.2) 805 (48.1) 853 (51.0)

4,032 (93.1) 4,101 (94.7) 3,947 (91.1) 2,200 (50.8) 2,247 (51.9)

0.515 0.985 0.283 0.064 0.539

<0.001

Statistical analyses were performed using R Statistical Software version 3.4.3 (R Foundation for Statistical Computing, Vienna, Austria).

RESULTS BASELINE

CLINICAL

CHARACTERISTICS. Among

patients with complex coronary artery lesion, 1,674 patients

(27.9%)

underwent

IVUS-guided

PCI,

whereas the remaining 4,331 patients (72.1%) underwent angiography-guided PCI. The mean age of the

Values are mean
SD or n (%). ACE ¼ angiotensin-converting enzyme; ARB ¼ angiotensin receptor blocker; LVEF ¼ left ventricular ejection fraction; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention.

total study population was 63.3
10.9 years, and 2,325 patients (38.7%) presented with acute coronary syndrome. Baseline clinical characteristics of the IVUS-guided PCI and angiography-guided PCI groups

In the multivariable models, we included the

are shown in Table 1. Compared with patients un-

covariates that were significant in univariate analysis

dergoing PCI with angiographic guidance, those with

or those that were clinically relevant. The adjusted

IVUS guidance were slightly younger; were more

HRs and 95% CIs were acquired by Cox regression

likely to be male; and were less likely to have car-

based on age, sex, hypertension, diabetes mellitus,

diovascular risk factors including hypertension, dia-

chronic kidney disease, previous history of PCI,

betes mellitus, chronic kidney disease, and previous

previous history of MI, cerebrovascular accident, left

history of PCI, MI, and cerebrovascular events. The

ventricular ejection fraction, acute coronary syn-

proportion of patients that presented with acute

drome, multivessel disease, left main coronary artery

coronary syndrome was significantly lower in the

involvement,

artery

IVUS-guided PCI group. Medical treatments after PCI

lesion

were similar between the 2 groups (Table 1).

involvement,

left

anterior

percent

descending

diameter

stenosis,

length, transradial approach, SYNTAX score, and angiographic success of PCI. For propensity-score

PROCEDURAL CHARACTERISTICS. Among the total

matching and IPW analysis, a full nonparsimonious

population with various complex lesion subsets,

model was developed to include all variables listed in

39.4% presented with bifurcation lesions, 25.4% with

Online Table 1. Procedural characteristics that might

CTO lesions, 10.2% with unprotected left main dis-

be affected by IVUS, including implanted stent num-

eases, 50.4% with long lesions, 9.2% with in-stent

ber, size, length, and maximum balloon pressure,

restenosis lesions, and 2.2% with heavily calcified

were excluded from the model. The covariate balance

lesions. Multivessel PCI and multiple stent implan-

after propensity-score matching or IPW adjustment

tation ($3 stents) were performed in 49.9% and 18.1%

was assessed by calculating the absolute standardized

of enrolled subjects, respectively. Table 2 presents

mean differences. Standardized mean differences

lesion and procedural characteristics according to

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IVUS usage. The mean percent diameter stenosis and total lesion length of the total study population were

T A B L E 2 Lesion and Procedural Characteristics in Patients With Complex Coronary

Artery Lesions Undergoing PCI According to Use of Intravascular Ultrasound

86.8
10.4% and 37.5
24.1 mm, respectively. Mul-

Intravascular Ultrasound–Guided Angiography-Guided (n ¼ 1,674) (n ¼ 4,331)

tivessel disease was more commonly observed and the mean number of treated lesions was significantly greater in the angiography-guided PCI group, but left main coronary artery or left anterior descending cor-

5

IVUS-Guided PCI for Complex Coronary Lesion

p Value

Lesion characteristics <0.001

Number of vessel disease

onary artery involvement was more frequently

1-vessel disease

501 (29.9)

1,110 (25.6)

observed and the SYNTAX score was significantly

2-vessel disease

758 (45.3)

1,824 (42.1)

3-vessel disease

415 (24.8)

1,397 (32.3)

1,273 (70.1)

3,221 (74.4)

0.001

greater in the IVUS-guided PCI group. Figure 2 presents usage proportion of IVUS according to lesion

Multivessel disease Lesion location (per vessel)

profiles. Among the complex lesions, IVUS was most

LM

453 (27.1)

231 (5.3)

<0.001

commonly used for left main disease (71.6%), fol-

LAD

1,406 (84.0)

3,417 (78.9)

<0.001

lowed by bifurcation lesions (46.8%).

LCX

842 (50.3)

2,679 (61.9)

<0.001

RCA

701 (41.9)

2,719 (62.8)

<0.001

guided PCI were more likely to have a longer fluo-

Number of lesion (per patient)

2.8
1.6

2.9
1.6

0.001

roscopy time, greater use of contrast volume, and

SYNTAX score

17.7
9.4

16.9
9.8

0.021

Pre-PCI diameter stenosis, %

83.9
11.1

88.0
10.0

<0.001

As shown in Table 2, patients undergoing IVUS-

lower frequency of transradial approach compared with those undergoing angiography-guided PCI. Conversely, angiographic success rates, implanted stent number, usage proportion of minimal stent diameter greater than 3 mm, usage proportion of post-dilatation, and maximum balloon pressure were significantly higher in the IVUS-guided group than in the angiography-guided group. The IVUS-guided PCI group also showed a significantly larger mean implanted stent diameter (IVUS vs. angiography, 3.2
0.4 mm vs. 3.0
0.4 mm; p < 0.001) and longer total stent length (46.2
26.8 mm vs. 44.3
24.4 mm; p ¼ 0.014) compared with the angiographyguided PCI group. In the IVUS-guided PCI group, IVUS was used only before PCI in 120 patients (7.2%), only post-stent in 240 patients (14.3%), and both pre-

Post-PCI diameter stenosis, % Total lesion length, mm

3.8
11.

8.7
19.4

<0.001

39.7
28.0

37.1
23.1

0.001

1,650 (98.6) 25.1
17.4 235.4
95.8 1,167 (69.7)

4,123 (95.2) 20.4
15.2 207.3
80.9 3,312 (76.5)

<0.001 <0.001 <0.001 <0.001 0.004

806 (48.1) 868 (51.9) 1.9
1.0 3.2
0.4 1,121 (67.0) 46.2
26.8 16.0
3.1 820 (49.0) 1,674 (100) 1,314 (78.5) 120 (7.2) 240 (14.3)

1,903 (43.9) 2,428 (56.1) 1.7
0.9 3.0
0.4 2,095 (48.4) 44.3
24.4 14.8
3.7 777 (17.9) 0 (0)

Procedural characteristics Angiographic success Fluoroscopy time, min Contrast volume, ml Transradial approach Type of stent First-generation drug-eluting stent Second-generation drug-eluting stent Implanted stent number Mean stent diameter, mm Minimal stent diameter $3 mm Total stent length, mm Maximum balloon pressure, mm Hg Adjunctive balloon dilatation Timing of intravascular ultrasound use Pre- and post-stent Pre-PCI only Post-stent only

<0.001 <0.001 <0.001 0.014 <0.001 <0.001 <0.001

and post-stent in 1,314 patients (78.5%) (Table 2). CLINICAL OUTCOMES. At least 1 year’s follow-up

data were available for 5,791 patients (96.4%) with a median follow-up duration of 64 months (inter-

Values are n (%) or mean
SD. LAD ¼ left anterior descending artery; LCX ¼ left circumflex artery; LM ¼ left main coronary artery; RCA ¼ right coronary artery; SYNTAX ¼ Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery; other abbreviation as in Table 1.

quartile range: 31–100). Compared with patients with angiography-guided PCI, those with IVUS-guided PCI

Cox proportional hazards model, IPW analysis, and

showed a significantly lower risk of cardiac death

propensity-score-matched

(10.2% vs. 16.9%; HR: 0.573; 95% CI: 0.460 to 0.714;

showed a significantly lower risk of adverse cardio-

p < 0.001) (Table 3, Figure 3). Similarly, all-cause

vascular events during follow-up in patients with

death, any MI, ischemia-driven TLR, definite or

IVUS-guided

probable ST, and major adverse cardiac event were

angiography-guided PCI (Table 3).

PCI

analysis,

compared

with

consistently

those

with

also significantly lower in the IVUS-guided PCI group

A landmark analysis explored the effects of IVUS-

than in the angiography-guided PCI group (Table 3,

guided PCI on both short-term and long-term

Online Figure 1). In particular, patients with IVUS-

follow-up clinical outcomes. Differences in the

guided PCI had significantly lower rates of MI

rates of cardiac death were prominent within 1 year

related to the target vessel compared with those with

after the index PCI, with continued divergence of

angiography-guided PCI; however, there was no sig-

the curves throughout the study period (Figure 4A).

nificant difference in the rate of MI related to the

Acute, subacute, and late ST were significantly

nontarget vessel between the 2 groups (Table 3).

lower in the IVUS-guided PCI group, but cumulative

Multiple sensitivity analyses, including multivariate

incidences of very late ST were similar between

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IVUS-Guided PCI for Complex Coronary Lesion

F I G U R E 2 Proportion of Use of IVUS According to Lesion Characteristics

Bar graphs show the proportion of use of IVUS with various lesion characteristics. The blue bars denote the proportion of use of IVUS, and the red bars denote the proportion of use of angiography only. CTO ¼ chronic total occlusion; ISR, in-stent restenosis; IVUS ¼ intravascular ultrasound; LM ¼ left main coronary artery; other abbreviation as in Figure 1.

the 2 groups (Figure 4B). Conversely, a significant

DISCUSSION

difference in ischemia-driven TLR between the 2 groups was only observed at long-term follow-up

The current study found beneficial effects of IVUS-

(Figure 4C).

guided PCI compared with angiography-guided PCI among patients with complex coronary artery lesions,

OUTCOME

DIFFERENCES

BETWEEN

IVUS-

AND

using data from a large scale, prospective institu-

ANGIOGRAPHY-GUIDED PCI ACCORDING TO SUBGROUP.

tional registry with long-term follow-up. This study

To evaluate the differential effects of IVUS-guided

has several principal findings (Central Illustration).

PCI compared with angiography-guided PCI for

First, patients with IVUS guidance underwent com-

various complex coronary artery lesions, we addi-

plex PCI with larger stent size, longer stent length,

tionally performed a subgroup analysis according to

more frequent post-dilatation, and higher maximum

lesion characteristics (Figure 5A). The beneficial effect

balloon pressure compared to those with angio-

of IVUS-guided PCI was consistent across various

graphic guidance alone. Second, compared with

complex lesion subsets. The greatest benefit of IVUS-

angiography-guided PCI, IVUS-guided PCI signifi-

guided PCI was found in left main coronary artery

cantly reduced the long-term risk of cardiac death in

disease (HR: 0.203; 95% CI: 0.126 to 0.329; p < 0.001)

patients with complex coronary artery lesions. In

among various complex lesion profiles.

addition, IVUS-guided PCI was associated with lower

Figure 5B presents a forest plot indicating the

risks of MI (especially MI related to the target vessel),

outcomes as related to various patient or procedural

ischemia-driven TLR, ST, and major adverse cardiac

characteristics. The lower risk of cardiac death in

event. Third, among various complex lesion subsets,

the IVUS-guided PCI group was similar across the

the greatest benefit of IVUS guidance was identified

various patient characteristics, without significant

in patients with left main coronary artery disease,

interaction. However, the absolute benefits of IVUS

although favorable outcomes of IVUS-guided PCI

guidance were significantly greater in the second-

were observed in most complex lesions. Fourth, the

generation

results were consistent across various subgroups. In

DES

era,

although

survival

benefits

of IVUS-guided PCI were observed in both the

particular, the benefits of IVUS guidance were more

first-generation and second-generation DES eras

apparent with the second-generation DES than with

(interaction p ¼ 0.008).

the first-generation DES.

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T A B L E 3 Comparison of Long-Term Clinical Outcomes Between Intravascular Ultrasound–Guided and Angiography-Guided PCI Among

Patients With Complex Coronary Artery Lesions Intravascular Ultrasound–Guided (n ¼ 1,674)

Angiography-Guided (n ¼ 4,331)

Univariate Analysis

Multivariable Analysis*

HR

95% CI

p Value

HR

95% CI

Cardiac death

98 (10.2)

416 (16.9)

0.573

0.460–0.714

<0.001

0.629

0.494–0.801

<0.001

p Value

All-cause death

173 (17.1)

686 (25.5)

0.610

0.516–0.721

<0.001

0.684

0.570–0.822

<0.001

Any MI Target vessel MI Nontarget vessel MI

56 (4.8) 39 (3.6) 17 (1.2)

213 (7.3) 144 (4.9) 69 (2.4)

0.640 0.666 0.590

0.477–0.859 0.468–0.949 0.347–1.003

0.003 0.025 0.051

0.650 0.609 0.754

0.470–0.898 0.411–0.903 0.426–1.332

0.009 0.013 0.330

Ischemia-driven TLR

86 (8.3)

275 (11.4)

0.750

0.589–0.956

0.020

0.764

0.586–0.995

0.046

Stent thrombosis‡

35 (3.1)

147 (4.4)

0.595

0.411–0.860

0.006

0.578

0.385–0.870

0.009

192 (18.5)

735 (28.1)

0.625

0.533–0.732

<0.001

0.646

0.543–0.769

<0.001

MACE† T A B L E 3 Continued

IPW Analysis HR

95% CI

PS Matched Analysis p Value

HR

95% CI

p Value

Cardiac death

0.780

0.691–0.879

<0.001

0.657

0.494–0.874

0.004

All-cause death

0.797

0.725–0.876

<0.001

0.672

0.545–0.829

<0.001

Any MI Target vessel MI Nontarget vessel MI

0.808 0.636 1.223

0.685–0.954 0.514–0.786 0.927–1.614

0.011 <0.001 0.154

0.645 0.588 0.825

0.442–0.941 0.376–0.919 0.402–1.692

0.023 0.020 0.600 0.008

Ischemia-driven TLR

0.788

0.681–0.913

0.002

0.664

0.491–0.900

Stent thrombosis‡

0.680

0.556–0.833

<0.001

0.517

0.329–0.810

0.004

MACE†

0.717

0.653–0.786

<0.001

0.657

0.537–0.805

<0.001

Values are n (%). Cumulative incidence of events was presented as Kaplan-Meier estimates. *Adjusted variables included age, sex, hypertension, diabetes mellitus, chronic kidney disease, previous history of PCI, MI, cerebrovascular accident, LVEF, acute coronary syndrome, multivessel disease, LM involvement, LAD involvement, % diameter stenosis, lesion length, transradial approach, SYNTAX score, angiographic success of PCI, and type of stent. †MACE was defined as a composite of cardiac death, myocardial infarction, ischemia-driven TLR, or stent thrombosis. ‡Stent thrombosis was defined as definite or probable. CI ¼ confidence interval; HR ¼ hazard ratio; IPW ¼ inverse-probability-weighted; MACE ¼ major adverse cardiac event(s); PS ¼ propensity-score; TLR ¼ target lesion revascularization; other abbreviations as in Tables 1 and 2.

Previous studies that compared IVUS-guided PCI

F I G U R E 3 Comparison of Long-Term Risk of Cardiac Death Between IVUS-Guided

with angiography-guided PCI have reported conflict-

Versus Angiography-Guided Percutaneous Coronary Intervention Among Patients

ing results, although several meta-analyses have

With Complex Coronary Artery Lesions

shown that IVUS-guided PCI was associated with significantly lower rates of adverse clinical events compared

with

angiographic

guidance

(22–24).

Therefore, the current guidelines recommend IVUS in selected patients to optimize stent implantation (18,19). Patients undergoing PCI for various complex coronary lesions could benefit the most from IVUS guidance.(17) However, data are limited regarding specific patients or lesions that can benefit from IVUS. Randomized controlled trials have demonstrated benefits of IVUS only with CTO, long lesions, or all-comers (12–14,25). Although the benefits of IVUS were especially evident in patients with complex coronary artery lesions according to data from the large prospective registry, the definition of complex disease included a relatively narrow spectrum of patients (11). Moreover, all of the previously mentioned studies reported only 1-year outcomes; long-term

Kaplan-Meier curves are shown for comparison of the rates of cardiac death between

results were not available. Therefore, we compared

IVUS-guided and angiography-guided percutaneous coronary intervention. Abbreviation

the effects of IVUS guidance with angiographic

as in Figure 2.

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F I G U R E 4 Time-Dependent Cox Analysis

Kaplan-Meier curves are shown for comparison of risk of cardiac death (A), stent thrombosis (B), and ischemia-driven target lesion revascularization (C) between IVUS-guided and angiography-guided percutaneous coronary intervention. The dashed line corresponds to the 1-year time-point for landmark analysis. CI ¼ confidence interval; HR ¼ hazard ratio; LRT ¼ likelihood ratio test; TLR ¼ target lesion revascularization; other abbreviation as in Figure 2.

guidance on long-term clinical outcomes in large

In the present study, IVUS-guided PCI, compared

populations undergoing PCI for complex lesions that

with angiography-guided PCI, significantly reduced

are generally accepted in clinical practice. Consid-

the long-term risk of cardiac death, target-vessel MI,

ering that proven efficacy and safety of second-

ischemia-driven TLR, and ST in patients with com-

generation DES with improved device deliverability

plex coronary artery lesions. Improvement of opti-

and conformability have led its use to complex lesion

mization of stent deployment by IVUS might explain

subsets increasingly, to improve outcomes of patients

our results (26). In accordance with previous studies,

undergoing PCI for complex lesions is of great

a larger stent size, longer stent length, higher pro-

importance.

portion

of

post-dilatation,

and

higher

inflation

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Choi et al. IVUS-Guided PCI for Complex Coronary Lesion

F I G U R E 5 Comparison of Long-Term Risk of Cardiac Death Between IVUS-Guided and Angiography-Guided PCI According to Subgroups

The cumulative incidence and hazard ratio with 95% confidence interval of cardiac death are presented between IVUS-guided and angiography-guided PCI according to various lesion characteristics (A) and patient or procedural characteristics (B). IHD ¼ ischemic heart disease; NSTE-ACS ¼ non–ST-segment elevation acute coronary syndrome; STEMI ¼ ST-segment elevation myocardial infarction; other abbreviations as in Figures 1, 2, and 4.

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C E NT R AL IL L U STR AT IO N Long-Term Clinical Outcomes Between IVUS-Guided and Angiography-Guided PCI for Complex Lesion

Procedural Factors P < 0.001

P = 0.014

P < 0.001

3 2 1

Max Balloon Pressure (atm)

80 Total Stent Length (mm)

Mean Stent Size (mm)

4

60 40 20

0

0 Intravascular Ultrasound-Guided PCI

20 15 10 5 0

Angiography-Guided PCI

Cumulative Incidence of Cardiac Death (%)

Clinical Outcomes 20 16.9%

Log rank p < 0.001

15 10.2%

10

5

0 0

1

2

3

4

5

6

7

8

9

All Lesion

0.573 (0.460-0.714)

Bifurcation Lesion

0.682 (0.498-0.934)

Chronic Total Occlusion Lesion

0.670 (0.408-1.102)

Left Main Coronary Artery Disease

0.203 (0.126-0.329)

Long Lesion

0.602 (0.450-0.804)

Multi-Vessel PCI

0.639 (0.473-0.864)

Multiple Stents Implantation

0.532 (0.332-0.855)

In-Stent Restenosis Lesion

0.837 (0.403-1.740)

Calcified Lesion

0.458 (0.052-4.012)

10

Time (Years) Intravascular Ultrasound

0.01

0.1

1

Favors Intravascular Ultrasound

10 Favors Angiography

Angiography

Choi, K.H. et al. J Am Coll Cardiol Intv. 2019;-(-):-–-.

The current study demonstrated the long-term clinical outcomes between intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) and angiography-guided PCI for patients with complex coronary artery lesion. The IVUS-guided PCI group showed larger implanted stent diameter, longer total stent length, and higher maximum balloon pressure compared with the angiography-guided PCI group. IVUS-guided PCI also had significantly lower risk of cardiac death compared with angiography guidance alone. Among the complex lesion profiles, IVUS-guided PCI was of greatest benefit in reducing risk of cardiac death in patients with left main disease. (Top) Bar graphs denote mean, and error bars denote SD.

pressures were found in patients undergoing IVUS-

optimization of PCI reduces ST by adequate stent

guided PCI compared with those with angiography-

expansion and by detection of suboptimal findings,

guided PCI, which might result in adequate stent

such as edge dissection or incomplete apposition, in

expansion and apposition, and full lesion coverage

the early period after the index procedure. Adequate

(9–11). Interestingly, a landmark analysis at 1 year

stent expansion and full lesion coverage might also

showed that IVUS-guidance had different effects on

contribute to a later reduction in TLR. It might have

individual outcomes. Although the reduction in ST

an influence on the reduction of heart failure aggra-

was prominent within 1 year after the index proced-

vation or ischemia-induced arrhythmic event with

ure, a significant reduction in TLR was observed only

unexplained sudden death, and be a possible reason

at follow-up beyond 1 year. These results suggest that

of difference for cardiac death at long-term follow-up.

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IVUS-Guided PCI for Complex Coronary Lesion

Taken together, these findings demonstrate a signif-

benefit with IVUS-guided PCI. It might be affected

icant difference in the risk of cardiac death between

by potential selection biases. Similar to previous

the 2 groups throughout the study period.

observational studies, our data showed patients who

The benefit of IVUS-guidance was consistent across

underwent angiography-guided PCI were more likely

various lesion subsets and subgroups. Especially, our

to have general cardiovascular risk factors compared

data showed IVUS-guided PCI was of greatest benefit

with

in reducing the risk of cardiac death in patients with

Although we performed multiple sensitivity analyses

left main coronary artery disease, among patients

including

with complex coronary artery lesion. This finding was

methods to reduce potential confounders, we could

in close agreement with a previously reported study,

not correct for unmeasured variables.

those

who

underwent

propensity-score

IVUS-guided

matching

and

PCI. IPW

focused on IVUS-guided PCI for left main lesions (27).

Second, choice of treatment strategy, vascular

In addition, significant interaction was observed be-

access, type of stent, and concomitant medications

tween the type of DES and IVUS-guidance. Although a

might have reflected the individual physician’s pref-

survival benefit of IVUS-guided PCI was observed in

erence. In particular, the decisions of whether to use

patients receiving first- and second-generation DES,

IVUS and how to apply the IVUS images for clinical

the benefits of IVUS-guidance were more prominent

practice were left to each operator’s discretion, with

in patients undergoing PCI with second-generation

no specific guidelines for optimal stent implantation.

first-generation

are

In case of multivessel PCI, to treat all lesions under

several potential explanations for this finding. First,

IVUS guidance or only the complex lesions under

compared

with

DES.

There

the improved stent profile of second-generation DES

IVUS guidance is also based on physician’s discretion.

has allowed interventional cardiologists to perform

Finally, this study included only patients from a sin-

more complex PCI, which may lead to greater benefits

gle center. Despite these limitations, the current

of IVUS-guidance in the second-generation DES era.

study had the advantages of long-term follow-up data

Second, in the first-generation DES era, IVUS may

collection, a large population, and strict control to

have been less beneficial because of the limitation of

adjust for confounding factors using multiple sensi-

the stent itself, even if stent optimization was per-

tivity analyses including propensity-score matching

formed using IVUS. Therefore, the use of IVUS for

and IPW methods.

stent optimization during complex PCI should be considered more strongly, even in the second-

CONCLUSIONS

generation DES era, which provides dramatically reduced stent related adverse events.

Among patients with complex coronary artery lesions

A major strength of the current study was enroll-

including bifurcation, CTO, left main disease, multi-

ment of all-comers with complex lesion and long-

vessel disease or multiple stent implantation, long

term follow-up duration, and comprehensive evalu-

lesion, in-stent restenosis, and calcified lesion, IVUS-

ation of the follow-up outcomes. Although a recent

guided PCI with DES was associated with the lower

meta-analysis documented that cardiac death, MI,

risk of long-term adverse events compared with

and ST were significantly lower in an IVUS-guided PCI

angiography-guided DES implantation. These results

group than in an angiography-guided PCI group, not

suggest that IVUS should be used to assess the lesion

all individual trials showed a statistically significant

characteristics and to optimize stent implantation when

difference in cardiac death rate (28). In contrast to

performing PCI with DES for complex coronary lesion.

previous trials, the current study showed that patients who underwent IVUS-guided PCI had a significantly lower risk of the hard endpoints including cardiac death, MI, and ST compared with those with angiography-guided PCI, even after adjustment for baseline differences using a vigorous statistical method.

ADDRESS FOR CORRESPONDENCE: Dr. Young Bin

Song, Division of Cardiology, Department of Medicine,

Heart

Vascular

Stroke

Institute,

Samsung

Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. E-mail: youngbin.song@gmail.

STUDY LIMITATIONS. First, because this study was

com. OR Dr. Joo-Yong Hahn, Division of Cardiol-

nonrandomized, confounding factors could have

ogy, Department of Medicine, Heart Vascular Stroke

affected the results. Especially, observational studies

Institute, Samsung Medical Center, Sungkyunkwan

or meta-analyses consistently show a mortality

University

benefit

Gangnam-gu,

for

IVUS-guided

PCI,

but

randomized

controlled trials consistently show a lack of mortality

School Seoul

of

Medicine,

06351,

E-mail: [email protected].

81

Republic

Irwon-ro, of

Korea.

11

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PERSPECTIVES WHAT IS KNOWN? IVUS can provide useful

and adverse cardiac events compared with angiography-

information on pre-intervention lesion characteristics,

guided PCI in patients who had a complex coronary artery

post-intervention optimal stent implantation, and

lesion.

possible complications after stent implantation. However, there have been limited data regarding impact of

WHAT IS NEXT? Future well-designed large

IVUS-guided PCI on long-term clinical outcomes in

randomized controlled trial for comparison with

patients undergoing complex procedures.

intravascular imaging guidance versus angiography guidance in patients with complex coronary artery lesion

WHAT IS NEW? IVUS-guided PCI was associated

should be addressed.

with significantly lower long-term risk of cardiac death,

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