Results and Long-Term Predictors of Adverse Clinical

Events After Elective Percutaneous Interventions on

Unprotected Left Main Coronary Artery
Takuro Takagi, MD; Goran Stankovic, MD; Leo Finci, MD; Konstantinos Toutouzas, MD;
Alaide Chieffo, MD; Vassilis Spanos, MD; Francesco Liistro, MD; Carlo Briguori, MD;
Nicola Corvaja, MD; Remo Albero, MD; Ginevra Sivieri, RN; Rossella Paloschi, RN;
Carlo Di Mario, MD; Antonio Colombo, MD

BackgroundThe safety and efficacy of percutaneous coronary intervention of de novo lesions in unprotected left main
coronary arteries remains an unresolved issue.
Methods and ResultsWe analyzed 67 consecutive patients treated with the following devices: 39 with stents, 12 with
rotational atherectomy plus stents, 13 with directional coronary atherectomy plus stents (a total of 64 patients were
treated with stents), and 3 patients with directional coronary atherectomy only. The reference vessel size was
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3.780.73 mm and lesion length was 6.63.0 mm. In-hospital complications were 2 coronary artery bypass grafts
(CABGs) (3.0%), 2 Q-wave myocardial infarctions (MIs) (3.0%), and 3 nonQ-wave MIs (4.5%); there were no deaths.
The estimated cardiac survival at 3 years was 91%. The cardiac mortality rate was higher in patients with Parsonnet
score 15 versus 15 (21.4% versus 4.2%, P0.02) at 3 years. The independent covariate of cardiac death was
preserved left ventricular ejection fraction; for combined cardiac events (cardiac death, MI, repeat revascularization) it
was large reference vessel size. Follow-up angiography at 52 months in 85% of eligible patients revealed 31.4%
restenosis. Extending the follow-up to 3123 months (19 patients with follow-up beyond 3 years) the cumulative event
rates were 11 deaths (16.4%), 8 of them cardiac (11.9%), 2 (3.0%) MI, and 16 (23.9%) repeat revascularizations (CABG
in 5 patients).
ConclusionsElective percutaneous coronary intervention of de novo lesions in left main coronary arteries is feasible,
with low procedural risk. The long-term follow-up revealed a high rate of angiographic restenosis and repeat
revascularization, with a relatively high incidence of cardiac death. Reference vessel size and left ventricular function
are the most important predictors of favorable follow-up. (Circulation. 2002;106:698-702.)
Key Words: angioplasty coronary disease revascularization stents survival

T he application of percutaneous coronary interventions

(PCI) has expanded beyond standard indications in
recent years as the result of the wide availability and use of
stents.1,2 Lesions in the left main coronary artery (LM) are
considered a standard indication for surgical revasculariza-
tion, on the basis of the results of randomized studies.3
Several recent reports using coronary stenting for unprotected
LM lesion showed encouraging follow-up clinical results
with this technique. The first published multicenter experi-
ence in 107 patients (ULTIMA Registry: Unprotected Left
Main Trunk Investigation Multicenter Assessment) including
both elective and emergent treatment4 showed an in-hospital
mortality rate of 12% and a cumulative 1-year mortality rate
of 29%, whereas recent studies in patients with elective
treatment reported very low hospital complications and a
1-year survival rate of 97% or higher.5 However, an updated
report from the ULTIMA Registry continued to show a high
in-hospital and follow-up mortality rates.6
One major problem is that many series include elective and
emergency interventions, making the results difficult to use
when recommending this procedure to a specific patient.
With the intent to provide further data in this controversial
field, we examined and report our complete experience with
elective percutaneous treatment of lesions involving unpro-
tected LM.
Methods
Patients and PCI
From April 1993 to June 2001, 67 consecutive patients with de novo
unprotected LM stenosis were electively treated in our institution.
Every patient had 50% diameter stenosis by visual estimate. The
decision to perform PCI versus surgery was considered when one of

Received March 20, 2002; revision received May 17, 2002; accepted May 21, 2002.
From EMO Centro Cuore Columbus, Milan, Italy (T.T., G.S., L.F., K.T., N.C., R.A., G.S., R.P., C.D.M., A.C.), and San Raffaele Hospital, Milan, Italy
(A.C., V.S., F.L., C.B., C.D.M., A.C.).
Correspondence to Antonio Colombo, MD, EMO Centro Cuore Columbus, 48 Via Buonarroti, 20145 Milan, Italy. E-mail columbus@micronet.it
2002 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/01.CIR.0000024983.34728.5D

698
 Takagi et al Outcomes After Elective PCI on Unprotected Left Main 699

the two conditions was present: (1) suitable anatomy and lesion TABLE 1. Baseline Patient Characteristics (n67)
characteristics for stenting and preference by the patient and by the
referring physician for a percutaneous approach, both of them being Age, y 6512
aware of the procedural risks; (2) suitable anatomy and lesion Male sex 56 (84)
characteristics for stenting and contraindication to surgery on the Cardiac risk factors
basis of the presence of comorbidity evaluated by a cardiac surgeon.
The Parsonnet surgical risk score7 8 was calculated for each patient, Hypertension 37 (55)
and patients were stratified in high and lowsurgical risk groups. Diabetes mellitus 6 (9)
Lesions underwent balloon predilation, rotational atherectomy, di- Cigarette use 31 (46)
rectional atherectomy, or intravascular ultrasound evaluation, ac-
Hypercholesterolemia 47 (70)
cording to the operators decision. Final stent implantation was
encouraged in most of the lesions. Unstable angina 27 (40)
Stents were deployed to achieve the best possible final lumen Previous MI 23 (34)
diameter.9,10 Preprocedural and postprocedural therapy consisted of
Three-vessel disease* 30 (45)
ticlopidine and aspirin.11
A clinical and angiographic follow-up was scheduled for all LVEF 0.570.13
patients. Clinical follow-up was performed at 1, 3, and 6 months and High risk by Parsonnet score (15) 19 (28)
at the latest follow-up time by clinic visits or by telephone interview
Values are given as number (%) or meanSD.
with the patients physician. Angiographic follow-up was scheduled
*Also right coronary artery disease.
at 6 months after successful procedure or earlier if noninvasive
evaluation or clinical presentation suggested the presence of
ischemia.
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Results
Definitions Immediate Results
Procedural success was defined as revascularization in the target Baseline clinical, angiographic, and procedural characteris-
lesion with 30% residual stenosis according to angiography and tics are summarized in Tables 1 and 2. The mean age of
with the patient leaving hospital free from any of the following patients was 6512 years (range, 30 to 86); 40% of patients
events: death, Q-wave or nonQ-wave myocardial infarction (MI), or had unstable angina. Almost half of the patients (45%) had
coronary artery bypass graft (CABG). NonQ wave MI was defined
as elevation of total CK 2 times above the upper limit of normal with
3-vessel disease. The site of the lesion in the LM was the
a positive MB fraction, in the absence of pathological Q waves. ostium in 22% of patients, the midportion of the artery in
The events analyzed for follow-up in this study were cardiac 18%, and the distal bifurcation in 60%. Angiographic success
death, CABG, MI (Q-wave and nonQ-wave), restenosis, and target was obtained in 65 patients (97%) and procedural success in
vessel revascularization (TVR), including ostium of left anterior
descending artery (LAD) and circumflex artery (LCx). Deaths were
classified as either cardiac or noncardiac. Deaths that could not be TABLE 2. Qualitative and Quantitative Angiographic
classified were considered to be cardiac related. Results (n67)
Restenosis was defined as 50% luminal narrowing at the target
Lesion location
site or ostium of the LAD and/or LCx demonstrated at the follow-up
angiography, irrespective of clinical symptoms of the patient. Ostium 15 (22)
Parsonnet score is a numeric scoring system used to stratify the Body 12 (18)
risk of death at 30 days in patients undergoing open heart surgery.7,8 Distal 40 (60)
The score is calculated as the sum of predefined numerical values
assigned to 15 different clinical risk factors (example: 1 for morbid Calcification 20 (30)
obesity and 20 for a second or subsequent reoperation). A score Eccentric 45 (67)
value 15 was chosen to express a risk 4%.7,8 Reference vessel diameter, mm 3.780.73
Lesion length, mm 6.63.0
Quantitative Coronary Angiography
The reference diameter, the stenosis length, and the minimal luminal Minimal lumen diameter, mm
diameter were determined with the use of a validated edge-detection Baseline 1.480.55
program (CMS version 4.0, MEDIS) at baseline, after procedure, and Final 3.770.70
at follow-up. The luminal indexes (eg, acute gain, late loss, loss
index, and so forth) were calculated according to the standard Follow-up 2.760.93
criteria. Diameter stenosis, %
Baseline 59.513.2
Statistical Analysis Final 4.09.7
Data were analyzed with commercial statistical programs (StatView
5, SAS Institute Inc). Continuous data are expressed as meanSD. Follow-up 26.620.0
For the analysis of continuous data, the Students t test was used to Acute gain, mm 2.230.73
assess differences between groups with and without clinical events. Late loss, mm 1.080.96
Categorical data were compared with the use of 2 or Fishers exact
tests. Cox proportional hazards model with the use of the stepwise Restenosis, diameter stenosis50%* 16 (31.4)
procedure was used to assess the correlates of events among multiple Ostium 2 (15.3)
clinical, procedural, and angiographic variables. Event-free survival Body 1 (14.3)
during follow-up at 3 years (72% of patients) was evaluated
according to the Kaplan-Meier method. A comparison of cardiac Distal 13 (41.9)
survival between low and highsurgical risk groups was performed Values are given as number (%) or meanSD.
by means of the log-rank test. *Restenosis includes ostium of LAD and LCx; npatients and/or lesions.
 700 Circulation August 6, 2002

TABLE 3. In-Hospital and Follow-Up Outcome (n67)

In-hospital outcome
Death 0
CABG 2 (3.0)
MI 5 (7.5)
Q-wave MI 2 (3.0)
NonQ-wave MI 3 (4.5)
Total MACE 6 (9.0)
Follow-up outcome
Death 11 (16.4)
Cardiac death 8 (11.9)
CABG 5 (7.5)
MI 2 (3.0)
TVR* 16 (24.6)
Total MACE at follow-up 23 (34.3) Figure 1. Kaplan-Meier curve showing freedom from major
Values are given as number (%). MACE indicates major adverse cardiac adverse cardiac events.
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events.
*TVR includes revascularization of ostium of LAD and LCx and excludes the
2 patients who underwent in-hospital CABG.
61 patients (91%). All patients with angiographic success had
complete revascularization. Stents were placed in 64 patients.
In 39 patients, stents were deployed after balloon angioplasty,
16 patients underwent directional coronary atherectomy
(stents were placed in 13 of them), and 12 patients had
rotational atherectomy and stenting. Intra-aortic balloon
pump was used in 58% of patients, intravascular ultrasound
was performed in 46%, and GP IIb/IIIa antagonists were used
in 15% of patients. Minimal lumen diameter increased from
1.480.55 mm before angioplasty to 3.770.70 mm after the
procedure, whereas mean diameter stenosis decreased from
5913% to 410%. Thirty-two patients (48%) also under-
went PCIs in the other major coronary segment in the same
procedure.
In-hospital complications occurred in 6 patients: There
were no deaths; 2 patients required emergency CABG, 2
patients had Q-wave MI, and 3 patients had nonQ-wave MI
(Table 3).
patients died: 8 of these patients had cardiac death (8 of 67;
11.9%). The characteristics of these patients and the time of
occurrence of death are presented in Table 4. The total event
rate at the end of the follow-up period, comprising cardiac
death, MI, and any revascularization, was 34.3%.
Angiographic follow-up was performed in 51 patients of
60 eligible (angiographic follow-up rate 85%) after 52
months. Angiographic restenosis was found in 16 patients
(31%). The specific location of the restenotic lesions accord-
ing to the LM segment originally involved are presented in
Table 2.
TVR was performed in 16 patients (11 repeat PCI and 5
CABG). Among these patients, 3 late (average, 16.7 months)
TVR were observed, all at the ostium of LAD or LCx. Figure
1 shows the Kaplan-Meier curve for freedom from major
adverse cardiac events (death, Q-wave MI, and TVR) limited
to 3 years. Event-free survival was 76% at 6 months, 71% at
1 year, and 62% at 3 years. By multivariate analysis,
reference vessel diameter was the only covariate of all cardiac
events at follow-up (hazard ratio, 0.36; P0.02; 95% CI, 0.15
to 0.87).

Follow-Up Cardiac Events Cardiac Deaths

After hospital discharge, patients completed a mean clinical In total, there were 11 deaths (16.4%), 8 of which were
follow-up of 3123 months (range, 5 to 94.7). Table 3 shows cardiac related. Six cardiac deaths occurred within 6 months
cardiac events during the follow-up period. A total of 11 after the procedure. The other two patients died 3 years

TABLE 4. Follow-Up Cardiac Death

Follow-Up Location of Bifurcation Reference Vessel
Age, Sex Duration, mo Lesion LVEF Involvement Diameter, mm
85, M 0.6 Distal 0.60 4.23
67, M 0.9 Distal 0.27 4.05
73, M 4.0 Distal 0.27 3.92
67, F 4.4 Ostium 0.68 4.48
62, M 5.0 Body 0.60 2.63
81, M 5.2 Distal 0.55 3.17
79, M 37.2 Distal 0.34 4.27
82, F 47.6 Body 0.35 3.49
 Takagi et al Outcomes After Elective PCI on Unprotected Left Main
Figure 2. Kaplan-Meier curve showing freedom from cardiac
death.
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after procedure, and both had low left ventricular ejection
fraction (LVEF) (0.35). Three noncardiac deaths were due
to cancer. The estimated cardiac survival rates at 1 and 3
years were 91% and 91%, respectively (Figure 2). By
multivariate analysis, the covariate of cardiac death was
LVEF 0.40 (hazard ratio, 8.6; P0.003; 95% CI, 2.2 to
34.8).
Cardiac mortality rate was higher in the patients with high
Parsonnet score (95.8% freedom from cardiac death at 3 years
in the low-risk group versus 78.6% in the high-risk group,
P0.021) (Figure 3).
Directional Atherectomy and Stenting for
Bifurcation Lesions
Forty patients had lesions involving the bifurcation of the left
main. Debulking with atherectomy was performed in 15, and
in 12 a stent was implanted. The angiographic restenosis rate
in these patients was 35.7% (5 of 14) and was not different
from patients who had stenting without debulking (47.1%, 8
of 17, P0.7). When we consider only the branch of the
bifurcation that underwent debulking, the restenosis rate was
23.5% (4 of 17).
Figure 3. Kaplan-Meier curves showing freedom from cardiac
death in patients with low and high surgical risk according to
Parsonnet score.
701
Discussion
The major findings in this study are (1) PCI with stenting of
lesions located in the LM is feasible in a variety of lesions
with high immediate clinical success; (2) at an average
follow-up time of 31 months there is an incidence of cardiac
death of 11.9% and of a need of TVR of 24.6%; (3) patients
with a high surgical risk by Parsonnet score have a 21.4%
3-year cardiac mortality rate compared with 4.2% in patients
with a low surgical risk; and (4) the most important predictor
of major adverse cardiac events during follow-up is the
reference vessel size of the LM, whereas LVEF 0.40 is the
only covariate of cardiac death.
Results of clinical follow-up of PCI performed on the LM
are inferior to the ones obtained after PCI in other locations.
An analysis of 4 recently published studies5,1214 addressing
elective LM interventions with stenting in most of the lesions
shows an incidence of in-hospital mortality rates ranging
from 0% to 4% for elective procedures, but cardiac mortality
rate increases to 13.7% when emergency PCIs are included.6
The long-term outcome in the same studies with a
follow-up time ranging from 7.3 to 25.5 months shows a
cardiac mortality rate between 0.7% to 5.7%, an incidence of
MI between 0% to 2.6%, and a need for revascularization
from 6.8% to 16.4%.
In these studies, the predictors of freedom from cardiac
events, including the need for revascularization, were angio-
graphic reference vessel size of the LM for the incidence of
restenosis5 and final lumen diameter for death.14 Our results
emphasize one important aspect of this type of procedure:
The hospital outcome is favorable, but the follow-up is
affected by a relatively high incidence of events such as
cardiac death, MI, and the need for reintervention. The fact
that 6 of 8 cardiac deaths occurred in the first 6 months
highlights the dramatic way restenosis could manifest when
PCI is performed on the LM and stresses that only a clear
improvement in this area will justify a wider application of
the PCI approach to LM disease. It could be argued that a
surgical approach could have avoided some of these early
deaths. Despite these valid concerns, we should consider that
LM disease carried a 15% mortality rate 5 years after surgical
revascularization in the Coronary Artery Surgery Study
(CASS).3 On the other side, we cannot dismiss that there are
improvements in surgical mortality rate, and it is difficult to
exactly estimate the surgical risk of this small cohort.
Along with the other investigators, we found favorable
outcome in patients with a low surgical risk. In our series,
patients (72% of total population) with a Parsonnet score 15
had 3-year cardiac mortality rate of 4.2%.
Despite these encouraging results in the group with unpro-
tected LM disease and low surgical risk, it is important to
consider that only a prospective study with a predefined
characterization of the low risk group will support this
preliminary finding.
The fact that there were predictors of long-term success
may help the selection of the most appropriate patient for this
type of procedure. The size of the reference vessel, a low
surgical risk, and a preserved left ventricular function5,14 are
the most important parameters to be considered.
 702 Circulation August 6, 2002
Unfortunately, the finding that patients with LM disease
and a high Parsonnet score or a low LVEF have the worst
prognosis undermines the value of PCI as an alternative to
surgery in these patients.
Another way to look at the practice of PCI of unprotected
LM is that in our series only 2 cardiac deaths occurred from
6 months to the end of follow-up (mean 3123 months). This
means that a solution to the problem of restenosis may
favorably affect the long-term outcome of this condition.
With regard to the value of atherectomy debulking before
stenting, we cannot draw any conclusion from our study,
most probably because of the small number of patients treated
with this approach, the tendency of the operator to use
atherectomy in the most complex bifurcations, and some
limitations in the ability to perform effective debulking in
both branches, especially with the old devices used in the
early time of this experience. It is interesting to notice that
the lowest numeric restenosis (4 of 17, 23.5%) was found
in the branch of a bifurcation in which debulking was
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performed before stenting.
On the basis of these data, we conclude that while awaiting
a solution to the problem of restenosis, elective PCI on
unprotected LM has good long-term results in patients with
low surgical risk and large reference vessel diameter.
Limitations
The most important limitation of this study is that this series
represents a selected group of patients with LM disease. The
fact that the procedures were performed over a long time
period introduces variables related to the evolution of devices
(more friendly stents) and operator experience. With regard to
the use of atherectomy, we need to take into account that this
approach was mostly used in bifurcations, making a compar-
ison with simple stenting difficult. The wide difference in
cardiac mortality rates among patients with low versus high
Parsonnet scores could be partially accounted for by chance,
as the result of our small sample size.
The fact that this study was not randomized versus surgery
is in our view a minor limitation because PCI of the LM is
still an approach in evolution and not yet ready for random-
ization versus an established technique such as CABG.
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 Results and Long-Term Predictors of Adverse Clinical Events After Elective Percutaneous
Interventions on Unprotected Left Main Coronary Artery
Takuro Takagi, Goran Stankovic, Leo Finci, Konstantinos Toutouzas, Alaide Chieffo, Vassilis
Spanos, Francesco Liistro, Carlo Briguori, Nicola Corvaja, Remo Albero, Ginevra Sivieri,
Rossella Paloschi, Carlo Di Mario and Antonio Colombo
Downloaded from http://circ.ahajournals.org/ by guest on June 13, 2017

Circulation. 2002;106:698-702; originally published online July 15, 2002;

doi: 10.1161/01.CIR.0000024983.34728.5D
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2002 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539

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