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Outcomes of Second Arterial Conduits in Patients Undergoing Multivessel Coronary Artery Bypass Graft Surgery
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 74, NO. 18, 2019
ª 2019 PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
Outcomes of Second Arterial Conduits in Patients Undergoing Multivessel Coronary Artery Bypass Graft Surgery Joanna Chikwe, MD,a,b Erick Sun, BA,a Edward L. Hannan, PHD,c Shinobu Itagaki, MD, MSC,a Timothy Lee, MD,a David H. Adams, MD,a Natalia N. Egorova, PHDd
ABSTRACT BACKGROUND Benefits of multiarterial versus single-arterial coronary bypass grafting (CABG) are debated. OBJECTIVES This study sought to compare long-term survival, morbidity, and graft patency after multiarterial versus single-arterial CABG. METHODS Mandatory clinical registries linked with discharge databases were used to identify baseline and operative characteristics and outcomes of 42,714 patients undergoing CABG from 2005 through 2012. Patients with single-vessel disease, without arterial conduits, or undergoing emergency, reoperative, or concomitant procedures were excluded. Survival, stroke, myocardial infarction, and repeat revascularization rates were compared using Cox modeling, and patients were matched by propensity score. Median follow-up was 7.8 years (interquartile range: 5 to 10 years); last follow-up was December 31, 2016. RESULTS Of the 26,124 patients, 3,647 (14.0%) underwent multiarterial CABG. Single-arterial CABG patients were older (mean 68 vs. 61 years; p < 0.001), had more comorbidities, and received fewer bypass grafts (3.4 vs. 3.6; p < 0.001). After adjusting for baseline differences, multiarterial CABG was associated with lower 10-year mortality compared with single-arterial CABG in 3,588 propensity-matched pairs (15.1% vs. 17.3%; p ¼ 0.01). Multiarterial CABG was associated with lower 10-year myocardial infarction (hazard ratio: 0.81; 95% confidence interval: 0.69 to 0.95) and lower 10-year reintervention rate (hazard ratio: 0.81; 95% confidence interval: 0.67 to 0.99). CONCLUSIONS In contemporary practice, single-arterial CABG is used in 85% of patients and is associated with increased long-term mortality, myocardial infarction, and reintervention compared with multiarterial CABG. Multiarterial CABG is underused in contemporary surgical revascularization, and targeted referral of younger patients for multiarterial revascularization may address this practice gap. (J Am Coll Cardiol 2019;74:2238–48) © 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.
A
rterial coronary bypass grafts have long been
compared in randomized clinical trials, which showed
associated with superior patency and sur-
no incremental survival benefit in intention-to-treat
vival compared with venous bypass grafts
analysis (3–7). Randomization is the only way to con-
alone in patients undergoing coronary artery bypass
trol for unmeasured confounding variables and selec-
graft (CABG) surgery (1,2). Outcomes of single-
tion bias, but such trials require many years to
arterial
generate adequate follow-up, involve highly selected
versus
multiarterial
CABG
have
been
Listen to this manuscript’s audio summary by Editor-in-Chief
From the aDepartment of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, New York, New York; bDepartment of
Dr. Valentin Fuster on
Surgery, The State University of New York, Stony Brook, New York; cSchool of Public Health, University at Albany, State University
JACC.org.
of New York, Albany, New York; and the dDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. The Icahn School of Medicine at Mount Sinai receives royalty payments for intellectual property from Edwards Lifesciences rand Medtronic. Dr. Chikwe has received speaker honoraria from Edwards Lifesciences. Dr. Adams has been a coprincipal investigator for trials for Medtronic and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Bernard J. Gersh, MB, ChB, DPhil, served as Guest Associate Editor for this paper. Manuscript received July 15, 2019; revised manuscript received August 13, 2019, accepted August 14, 2019.
ISSN 0735-1097/$36.00
https://doi.org/10.1016/j.jacc.2019.08.1043
JACC VOL. 74, NO. 18, 2019
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Multiarterial Versus Single-Arterial CABG
2239
patients and surgeons, and are commonly underpow-
missing personal or surgeon identifiers and
ABBREVIATIONS
ered to detect important clinical differences (8,9).
patients from out of state were excluded. The
AND ACRONYMS
Analysis of clinical registries can yield additional
Open Heart Surgery Registry was used to
relevant information, such as longer-term outcomes
identify baseline characteristics, the number
in much larger populations more representative of
of arterial and venous conduits, and incom-
clinical practice, with sufficient power to permit sub-
plete revascularization, which was defined as
group analysis of specific patient populations and
more diseased territories than the number of
practice patterns
grafts placed (Online Table 2).
(10,11). Our objective was to
CABG = coronary artery bypass grafting
CI = confidence interval HR = hazard ratio LAD = left anterior descending coronary artery
compare the long-term clinical and angiographic out-
SURGEON CRITERIA. We performed a sub-
comes of single-arterial and multiarterial CABG in
PCI = percutaneous coronary
group analysis to reduce the effect of surgeon
intervention
contemporary clinical practice.
expertise on outcomes. This involved applying
METHODS
surgeon-specific case volume thresholds similar to those used in randomized controlled trials and
STUDY DESIGN. This retrospective cohort analysis
observational studies (8,12). In this subgroup anal-
compared outcomes of patients with multivessel
ysis, patients were excluded if their surgeon had
coronary disease receiving single-arterial versus
performed <100 CABG procedures before the index
multiarterial CABG between January 1, 2005, and
CABG procedure. A total of 76 of 97 surgeons per-
December 31, 2012, in New Jersey. Patients were fol-
forming single-arterial, and 31 of 97 surgeons per-
lowed up to December 31, 2016. The study was
forming
approved by institutional review boards at the New
volume threshold for this analysis. The median
Jersey Department of Health and the authors’ in-
number of CABGs completed in the last 365 days by
stitutions, including a waiver of informed consent.
these surgeons at the time of the index procedure was
REGISTRIES. A clinical database, the mandatory state
Open Heart Surgery Registry, was used to identify patients, baseline clinical characteristics, and opera-
multiarterial
CABG
met
the
minimum
91 for single-arterial CABG, and 34 for multiarterial CABG, respectively. SEE PAGE 2249
tive variables. Under the oversight of the Department of Health, data on every individual patient undergo-
STUDY ENDPOINTS. The primary endpoint was all-
ing cardiac surgery are collected by clinical staff at all
cause mortality, identified from 4 separate sources,
hospitals performing cardiac surgery in the state. In-
including the New Jersey Vital Statistics death regis-
dividual charts are sampled to audit the quality of
try, and discharge disposition on the Open Heart
data collection quarterly, and external medical audi-
Registry, the Cardiac Catheterization Registry, and
tors verify data annually.
the New Jersey Discharge Data Collection System.
Long-term clinical outcome and graft patency data
There was near 100% agreement in deaths identified,
were obtained for individual patients by linking this
and for the few discrepant dates, the earliest date of
clinical registry with 3 Department of Health manda-
death reported was used. The date of last follow-up
tory databases using deterministic matching with a
was December 31, 2016, for all outcomes, except for
98% success rate. These were the New Jersey Cardiac
cardiac catheterizations, where the last available
Catheterization Registry, the New Jersey Discharge
follow-up was December 31, 2012. Secondary out-
Data Collection System (an administrative database
comes included stroke, myocardial infarction, repeat
containing data on all inpatient episodes from 1994
revascularization, and graft patency. Stroke was
and outpatient visits from 2004), and the New Jersey
defined as permanent neurological deficit due to an
Vital Statistics deaths registry, which contains all
ischemic or hemorrhagic cerebrovascular event, not
deaths known to any state or federal agency for New
including transient ischemic attacks. Repeat revas-
Jersey residents. Online Table 1 provides additional
cularization was defined as a post-operative redo
details.
CABG or percutaneous coronary intervention (PCI).
STUDY POPULATION. All patients undergoing iso-
lated multivessel CABG were included. Exclusion criteria were concomitant or previous cardiac surgery, hemodynamic instability (pre-operative shock, cardiopulmonary resuscitation, or inotrope require-
Native vessel and bypass conduit patency was determined by identifying patients with reports of stenosis >50% in any coronary angiography performed after the index CABG operation, through linkage with the New Jersey Cardiac Catheterization Registry.
ment), emergency status, and no arterial conduit use.
STATISTICAL ANALYSIS. Continuous variables are
In order to ensure complete follow-up, patients with
reported as mean SD. Categorical variables are
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F I G U R E 1 Patient Selection Flow Diagram
Initial Cohort • all patients who underwent CABG from 2005-2012 in New Jersey State n = 42,714
Exclusion Criteria: • single bypass graft (n = 4,891) • no arterial graft (n = 5,581) • no internal mammary artery graft (n = 778) • emergency status (n = 1,589) • hemodynamic instability (n = 924) • concomitant cardiac surgery (n = 9,921) • previous cardiac surgery (n = 1,329) • missing data (n = 299)
Final Total Cohort n = 26,124
Multi-Arterial Revascularization n = 3,647 (14.0%)
Single Arterial Revascularization n = 22,477 (86.0%)
CONSORT style diagram showing study patient cohort according to inclusion and exclusion criteria. CABG ¼ coronary artery bypass grafting.
expressed as proportions. Baseline characteristics
outcome, multiarterial revascularization was incor-
were compared using Student’s t-test for normally
porated as a dichotomous variable (13,14). Covariates
distributed continuous variables, Wilcoxon’s rank
adjusted for included patient age, sex, race, payer,
sum test for non-normally distributed continuous
year of surgery, body mass index, renal dysfunction,
variables, and Pearson’s chi-square test for categori-
pulmonary disease, hepatic dysfunction, prior or
cal
current
variables.
Comparisons
between
propensity-
malignancy;
cardiovascular
risk
factors
matched groups were performed with standardized
including diabetes, smoking, history of cerebrovas-
differences, paired Student’s t-test, and McNemar’s
cular disease including prior stroke, peripheral
chi-square test.
vascular disease, congestive heart failure, hyperten-
Kaplan-Meier analysis was used to estimate prob-
sion, atrial fibrillation, previous myocardial infarc-
ability of survival, and comparisons were performed
tion, previous PCI, left ventricular ejection fraction,
with the log-rank test (Online Figure 1). Competing
left main stem stenosis, number of diseased vessels,
risk analysis was used to estimate cumulative event
number of total anastomoses, use of cardiopulmo-
rates for myocardial infarction, stroke, repeat revas-
nary
cularization, and graft patency with the competing
beta-blockers, aspirin, statins, glycoprotein IIb/IIIa
event of death. Comparisons were performed with
inhibitors, adenosine diphosphate inhibitors, and
the Fine-Gray test. Hazard ratios (HR) were obtained
warfarin (see Online Table 1 for definitions). We
using Cox proportional hazard models. Given the
controlled for clustering of patients by surgeon and
possibility of repeated events for revascularization
hospital using a marginal Cox approach with a robust
when patients had multiple grafts, we performed
sandwich variance estimator. Additionally, individ-
bypass;
and
the
use
of
pre-operative
additional analysis using the Anderson-Gill model to
ual surgeon case volume was adjusted for, first, by
analyze risk of recurrent revascularization. For each
including annual volume as a covariate in the
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T A B L E 1 Baseline Characteristics of Patients Undergoing Single- Versus Multiple-Arterial Revascularization
All
Propensity Matched
Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
66.7 10.6
67.6 10.3
75.7
74.3
34.2 8.2
Hypertension Diabetes mellitus
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
Standardized Difference (%) p Value
60.8 10.5
<0.001
61.1 10.2
60.9 10.4
1.7
85.0
<0.001
85.0
84.8
0.7
0.7
34.2 8.2
34.4 8.7
0.1
34.5 8.2
34.4 8.8
1.2
0.6
92.4
93.0
89.0
<0.001
90.1
89.3
2.6
0.3
47.0
48.1
40.3
<0.001
40.3
40.6
0.7
0.8 0.9
Demographics Age, yrs Male BMI, kg/m2
0.5
Comorbidities
Peripheral vascular disease
17.0
17.5
13.8
<0.001
13.9
13.9
0.07
Tobacco use
63.5
63.7
61.7
0.02
62.1
61.7
0.8
0.7
Atrial fibrillation
28.4
29.5
21.4
<0.001
21.3
21.6
0.7
0.8
Heart failure
26.4
27.7
18.8
<0.001
18.9
19.0
0.4
0.9
Previous MI
47.4
47.9
43.7
<0.001
44.0
43.8
0.5
0.8
Previous PCI
24.4
24.4
24.1
0.7
23.9
24.3
0.9
0.7
Cerebrovascular accident
8.0
8.4
5.9
<0.001
6.0
6.0
0.0
0.9
COPD
25.1
25.7
21.5
<0.001
21.9
21.7
0.3
0.9
Renal failure (Cr >2.3 mg/dl)
3.4
3.8
1.4
<0.001
1.6
1.5
1.2
0.5
Dialysis
2.3
2.5
1.0
<0.001
1.1
1.1
0.6
0.7
Liver disease
2.1
2.2
1.6
0.02
1.7
1.6
0.6
0.8
Cancer
7.2
7.6
4.6
<0.001
5.1
4.7
1.9
0.4
49.8 12.2
49.6 12.4
51.0 10.9
<0.001
50.6 11.6
50.9 11.0
0.7
0.3
11.3
11.9
8.0
<0.001
8.8
8.1
0.7
0.4
35%–50%
43.7
43.9
42.7
43.3
42.8
0.06
>50%
44.9
44.2
49.4
47.9
49.1
0.4
2.5 0.9
2.5 0.9
2.5 0.8
0.7
2.5 0.8
2.5 0.8
0.6
0.8
I
11.8
11.9
11.0
0.3
10.3
11.1
1.1
0.7
II
36.9
36.8
37.4
38.4
37.5
1.6
III
38.7
38.6
39.5
39.4
39.4
2.2
IV
12.6
12.7
12.1
11.9
12.0
1.9
38.9
39.4
0.2
61.1
60.7
0.2
Pre-operative condition Ejection fraction <35%
NYHA functional class
Status Elective
35.0
34.2
39.3
Urgent
65.0
65.8
60.7
<0.001
0.7
Values are mean SD or %, unless otherwise indicated. BMI ¼ body mass index; COPD ¼ chronic obstructive pulmonary disease; Cr ¼ creatinine; MI ¼ myocardial infarction; NYHA ¼ New York Heart Association; PCI ¼ percutaneous coronary intervention.
models, and second, by performing a subgroup
on
analysis within which inclusion criteria included a
matched cohort, we fit a Cox model for mortality,
long-term
mortality
among
the
propensity-
minimum threshold individual surgeon case volume
adjusting for all measured covariates and controlling
of 100 of the index-case type.
for patients clustered within matched pairs (15,16).
Propensity score matching was used to compare
Besides a subgroup analysis based on surgeon vol-
mortality and secondary endpoints in single-arterial
ume, a number of subgroup analyses were per-
and multiarterial patients with similar characteris-
formed on the basis of age, ejection fraction, and the
tics (14,15). Propensity score was calculated using
type of the second arterial conduit (radial vs. inter-
logistic regression fit for multivessel CABG, adjust-
nal mammary artery), and comparing patients un-
ing for all measured covariates, with patients clus-
dergoing
tered within hospital. The C-statistic for the model
revascularization (Online Tables 3 to 5 and Online
single-arterial
versus
total-arterial
was 0.78. Matching was performed one-to-one with
Figures 2 to 6).
a caliper width of 0.10 of logit of the propensity
All tests were 2-tailed, and an alpha level of 0.05
score. To quantify the effect of multiarterial CABG
was considered statistically significant. All statistical
2241
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T A B L E 2 Operative Characteristics of Patients Undergoing Single Versus Multiple Arterial Revascularization
All
Left main disease
Propensity Matched
Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
36.8
37.2
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
Standardized Difference (%)
p Value
34.2
<0.001
34.8
34.2
0.8
0.6
Vessel disease 2.8 0.4
2.8 0.4
2.8 0.4
0.2
2.8 0.4
2.8 0.4
0.8
0.6
2-vessel disease
17.8
17.9
17.0
0.2
17.5
17.1
0.8
0.6
3-vessel disease
82.2
82.1
83.0
82.5
92.9
0.8
Total diseased vessels
Vessel disease by pre-operative angiographic data 2.7 0.5
2.7 0.5
2.7 0.5
0.9
2.7 0.6
2.7 0.6
1.7
0.6
2-vessel disease
22.4
22.4
22.3
0.9
22.1
22.4
3.1
0.7
3-vessel disease
76.0
75.9
76.0
75.8
75.9
2.7
3.4 0.9
3.4 0.9
3.6 1.0
<0.001
3.6 1.0
3.6 1.0
3.4
1.2 0.5
1.0 0
2.3 0.6
<0.001
1.0 0
2.3 0.6
Total diseased vessels
Total anastomoses Arterial
0.4 <0.001
IMA
1.1 0.4
1.0 0.03
1.8 0.7
<0.001
1.0 0.02
1.8 0.7
<0.001
Radial
0.1 0.3
0.001 0.04
0.5 0.6
<0.001
0.003 0.06
0.5 0.6
<0.001
2.2 1.0
2.4 0.9
1.3 1.0
<0.001
2.6 1.0
1.3 1.0
Incomplete revascularization
7.9
8.1
6.9
0.01
7.8
6.9
2.5
0.2
On-pump CABG
71.5
75.1
49.5
<0.001
49.4
50.2
2.7
0.5
107 55
107 55
106 56
0.4
106 56
106 56
2.4
0.8
Venous
Surgeon volume/year
<0.001
Values are % or mean SD, unless otherwise indicated. CABG ¼ coronary artery bypass grafting; IMA ¼ internal mammary artery.
analyses were performed using SAS version 9.4 (SAS
the number of bypass grafts performed was signifi-
Institute, Cary, North Carolina).
cantly higher, and the rate of incomplete revascularization
RESULTS
was
lower
in
patients
undergoing
multiarterial revascularization (Table 2). The individual mean annual surgeon volume during the
PATIENTS. The overall study cohort included 42,714
study period was 107 CABG operations and was not
patients who underwent CABG between January 1,
significantly different for single-arterial versus mul-
2005, and December 31, 2012. After excluding patients
tiarterial CABG patients (Figure 2). Propensity score
undergoing single-vessel bypass (n ¼ 4,891, 11.5%),
matching produced 3,588 matched patient pairs,
vein grafts only (n ¼ 5,581, 13.1%), no use of an in-
with standardized differences <5% for all baseline
ternal mammary artery conduit (n ¼ 778, 1.8%),
variables (Table 1).
emergency surgery (n ¼ 1,589, 3.7%), hemodynamic
SURVIVAL. In the overall cohort, multiarterial CABG
instability (n ¼ 924, 2.2%), concomitant surgery
was associated with lower mortality at 10 years
including any valve, aortic, or vascular procedure
compared with single-arterial CABG (15.0% vs. 26.0%;
(n
¼
9,921,
23.2%),
previous
cardiac
surgery
adjusted HR: 0.84; 95% confidence interval [CI]: 0.76
(n ¼ 1,329, 3.1%), and patients with missing data
to 0.92; p < 0.001) (Online Figure 1). Multiarterial
(n ¼ 299, 0.7%), 26,124 patients remained, consisting
CABG was associated with lower 10-year mortality
of 22,477 (86.0%) single-arterial and 3,647 (14.0%)
compared
multiarterial CABG patients (Figure 1).
propensity-matched pairs (15.1% vs. 17.3%; p ¼ 0.01)
Table 1 shows selected characteristics of the study patients
(all
variables
are
provided
in
with
single-arterial
CABG
in
3,588
(Central Illustration). There were 15,697 patients #70
Online
years of age (12,752 single-arterial revascularization,
Table 2). There were substantial differences in
2,945 multiarterial revascularization; 2,886 propensity-
baseline patient characteristics: multiarterial CABG
matched pairs) and 10,427 patients >70 years of age
patients were on average 7 years younger, much
(9,725 single-arterial revascularization, 702 multi-
more likely to be male, and with much less comor-
arterial revascularization; 688 propensity-matched
bidity, including significantly lower rates of dia-
pairs). When patients were stratified by age, multi-
betes, peripheral vascular disease, heart failure, and
arterial CABG was associated with lower 10-year
prior myocardial infarction (Table 1). Additionally,
mortality compared with single arterial CABG in
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Multiarterial Versus Single-Arterial CABG
Rate of Multi-Arterial Revascularization by Surgeon (%)
F I G U R E 2 Rates of Multiarterial Revascularization by Individual Surgeon Annual Case Volume
100 90 80 70 60 50 40 30 20 10 0 0
50
150
100 Surgeon CABG Volume/Year
95% Confidence Limits
95% Prediction Limits
Individual surgeon rates of multiarterial revascularization in New Jersey between 2005 and 2012, showing very wide practice variation, and no significant relationship between surgeon case volume and rates of multiarterial revascularization. Individual dots represent individual surgeon’s annual case volume. Lines represent 95% confidence limits. CABG ¼ coronary artery bypass grafting.
patients #70 years of age (adjusted HR: 0.87; 95% CI:
0.98; p ¼ 0.01) at 10 years in the overall cohort, and in
0.77 to 0.99), but not in patients >70 years of age
the propensity-matched cohort (6.6% vs. 8.1%;
(adjusted HR: 0.91; 95% CI: 0.75 to 1.1). The survival
p ¼ 0.02) (Figure 3A and Online Figure 2). Likewise,
benefit was similar in subgroup analysis based on
the rate of repeat revascularization was significantly
individual surgeon volume $100 index cases, which
lower in the propensity-matched cohort (11.5% vs.
single-arterial,
13.5%; HR: 0.86; 95% CI: 0.75 to 0.98; p ¼ 0.02)
2,931 multiarterial; 2,887 propensity-matched pairs)
(Figure 3B and Online Figure 3). The rate of stroke was
(adjusted
included
24,992
patients
(21,991
0.95;
significantly lower (4.1% vs. 6.4%; p < 0.001) in
p ¼ 0.005), but was not significant when restricted
multiarterial versus single-arterial CABG in the over-
only to patients with ejection fraction #30% (n ¼
all cohort but did not reach statistical significance in
2,777:
propensity-matched
HR:
2,513
0.83;
single
95%
arterial,
CI:
0.73
264
to
multiarterial;
262 propensity-matched pairs) (adjusted HR: 0.95; 95% CI: 0.68 to 1.3; p ¼ 0.80) (Online Figure 7).
patients
(4.2%
vs.
5.1%;
p ¼ 0.06) (Figure 3C and Online Figure 3). In a subgroup analysis of symptom-driven postoperative angiography, we compared patients with
SECONDARY OUTCOMES. The incidence of myocar-
single- versus total-arterial revascularization because
dial infarction was significantly lower after multi-
this was the only way to reliably ensure we were
arterial CABG compared with single-arterial CABG
comparing artery versus vein for the non-left anterior
(6.7% vs. 8.6%; adjusted HR: 0.85; 95% CI: 0.73 to
descending coronary artery (LAD) conduit. In this
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C E N T R A L IL L U ST R A T I O N Long-Term Mortality After Multiarterial Versus Single-Arterial Coronary Artery Bypass Grafting
35
HR 0.80 (95% CI 0.72 to 0.90) Fine-Gray p = 0.006
30 Mortality Probability (%)
2244
25 20 15 10 5 0
Multi-Arterial Single-Arterial
0
2
4
6 8 Years Since Surgery
3,588 3,588
3,459 3,437
3,339 3,317
2,655 2,646
1,745 1,706
10
12
867 822
427 412
Chikwe, J. et al. J Am Coll Cardiol. 2019;74(18):2238–48.
Long-term mortality is shown after multiarterial versus single-arterial coronary artery bypass grafting in 3,588 propensity-matched patient pairs. A significant survival benefit with multiarterial revascularization at 12 years (p ¼ 0.006) is shown. CI ¼ confidence interval; HR ¼ hazard ratio.
subgroup analysis, there were 215 non-LAD grafts
indicates that these groups were well matched
overall (140 internal mammary, and 75 radial arteries)
for differences in baseline characteristics and that
and 211 non-LAD grafts after propensity matching (139
the impact of unmeasured covariates was not
internal mammary and 72 radial arteries). The time to
substantial.
>50% stenosis in non-LAD grafts was shorter in single-arterial CABG compared with total-arterial
DISCUSSION
CABG patients in the overall cohort (adjusted HR: 0.89; 95% CI: 0.68 to 1.2; p ¼ 0.06) (Figure 4). When
In a contemporary multicenter cohort of patients
evaluating non-LAD grafts only, the rate of repeat PCI
undergoing CABG, which included long-term clinical
was significantly lower in arterial grafts (adjusted HR
and angiographic follow-up, the long-term risks of
of arterial graft vs. venous graft: 0.08; 95% CI: 0.03 to
myocardial infarction and death associated with
0.2; p < 0.001) and significantly higher in native
single-arterial CABG were higher than those associ-
vessels (adjusted HR of native vessel vs. venous graft:
ated with multiarterial CABG. Venous bypass grafts
5.5; 95% CI: 4.5 to 6.8; p < 0.001 in the overall cohort
exhibiting >50% stenosis were more likely to undergo
and in propensity-matched patients) (Figure 5).
repeat revascularization via percutaneous interven-
The 30-day mortality and major complications are
tion in symptom-guided post-operative angiographic
shown in Table 3: the lack of significant difference
follow-up than arterial conduits. Single-arterial CABG
between
was also associated with increased rates of repeat
propensity-matched
treatment
groups
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Multiarterial Versus Single-Arterial CABG
2245
F I G U R E 3 Cumulative Incidence of Secondary Outcomes in Propensity-Matched Patients
Cumulative Probability of Myocardial Infarction (%)
20
Cumulative Probability of Re-Intervention (%)
B
A
Adjusted Cox HR 0.81 (95% CI 0.69 to 0.95) Fine-Gray P = 0.02
15
10
5
0 0 Multi-Arterial Single-Arterial
3,588 3,588
2
4
3,389 3,356
6
8
10
Years Since Surgery 3,234 2,543 1,651 3,198 2,518 1,598
20
Adjusted Cox HR 0.86 (95% CI 0.75 to 0.98) Fine-Gray P = 0.02
15
10
5
0
820 755
2
0
12 Multi-Arterial Single-Arterial
405 375
3,588 3,588
4
6
8
Years Since Surgery 3,068 2,385 1,539 3,014 2,355 1,482
3,270 3,230
10
12
764 709
374 347
C Cumulative Probability of Stroke (%)
15
Adjusted Cox HR 0.81 (95% CI 0.64 to 1.0) Fine-Gray P = 0.07
10
5
0 0 Multi-Arterial Single-Arterial
3,588 3,588
2
4
3,425 3,396
6
8
Years Since Surgery 3,283 2,593 1,686 3,237 2,571 1,645 Multi-Arterial
10
12
832 788
410 392
Single-Arterial
Time-to-event curves showing cumulative incidence of (A) myocardial infarction, (B) repeat revascularization, and (C) stroke in propensity-matched patients undergoing single-arterial versus multiarterial coronary artery bypass grafting, with significantly higher rates of myocardial infarction (p ¼ 0.02) and repeat revascularization (p ¼ 0.02) in patients who underwent single compared with multiarterial revascularization. CI ¼ confidence interval; HR ¼ hazard ratio.
revascularization, including both repeat CABG and
single-arterial CABG was used in patients who tended
PCI, compared with multiarterial revascularization.
to be older with more comorbidity, and the technique
Our findings provide data that supplement the
was also associated with fewer grafts and increased
findings of prior comparative studies. These include
risk of incomplete revascularization. To the best of
>100 observational analyses, most of which have
our knowledge, our analysis is one of the first to
suggested
adjust
a
survival
benefit
from
multiarterial
for
all
these
factors
including
using
revascularization, and several randomized controlled
pre-operative angiographic data to account for dif-
studies that showed no benefit in intention-to-treat
ferences in completeness of revascularization. The
analysis (2–8,10,11). The major limitation of observa-
lack of a significant difference in major post-operative
tional studies are confounding variables arising from
morbidity at 30 days indicates that the impact of
selection bias, which cannot be completely adjusted
hidden confounders is likely to be very small. It has
for in a retrospective analysis (16). In our cohort,
been suggested that hidden confounders may explain
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linked to reduced long-term survival in an over-
F I G U R E 4 Cumulative Incidence Estimates for Detection of 50% Stenosis
lapping study cohort (17). There has been 1 large, multicenter, randomized
A Cumulative Probability of 50% Non-LAD Re-Stenosis (%)
50
study and a meta-analysis of randomized trials
Adjusted Cox HR 0.89 (95% CI 0.68 to 1.2) Fine-Gray P = 0.06
comparing single-arterial with multiarterial CABG (3,4). These trials have not typically been powered to
40
detect differences in mortality rate; instead, they have been based on composite outcomes including
30
death, myocardial infarction, and repeat revascularization. For example, ART (Arterial Revascularisation
20
Trial), a large randomized trial comparing outcomes of bilateral and single internal mammary artery, re-
10
ported 10-year mortality of 20.3% in the multiarterial group and 21.2% in the single-arterial CABG group
0
Single-Arterial (Vein Graft) Total-Arterial (Arterial Graft)
(p ¼ 0.62) (3). It would have required >20,000 pa-
0
2
4 Years Since Surgery
6
8
6,662
5,192
3,583
1,640
743
ence with an a of 0.05. The negative findings of the
215
170
135
82
44
ART trial have been attributed to the high rate of
tients to have an 80% power of detecting this differ-
crossover (13.9%) from bilateral to single internal
B Cumulative Probability of 50% Non-LAD Re-Stenosis (%)
50
mammary artery and the use of an additional arterial
HR 0.69 (95% CI 0.38 to 1.2) Fine-Gray P = 0.2
graft in 21.8% of the single internal mammary artery patients (8–10). Additionally, surgeon experience
40
may be a potential confounding variable, with lower experience associated with reduced use of and worse
30
outcomes with multiarterial revascularization. Our current study was designed to minimize the impact of
20
these limitations. Despite an abundance of high-quality data that
10
have helped define the patients who benefit from surgical revascularization with left internal mammary
0
to LAD anastomosis, the optimal surgical strategy for
0
2
4 Years Since Surgery
6
8
Single-Arterial (Vein Graft)
264
224
167
76
39
Observational and experimental data support use of a
Total-Arterial (Arterial Graft)
211
167
132
79
44
second arterial conduit, but the limitations of these
Single-Arterial (Vein Graft)
other coronary territories remains controversial.
Total-Arterial (Arterial Graft)
analyses are well recognized, and given the equivocal findings of randomized studies, consensus guidelines
Cumulative incidence estimates for detection of 50% stenosis are based on post-
place the lowest recommendations for use of multi-
operative angiographic follow-up in single versus total-arterial coronary bypass surgery.
arterial
Time-to-event curves showing competing risk of development of 50% stenosis in non-
compelling data and guidelines, combined with the
left anterior descending coronary artery bypass grafts in single versus total arterial revascularization patients with post-operative angiographic follow-up in (A) all pa-
revascularization
(18,19).
This
lack
of
incremental technical considerations and associated
tients (n ¼ 6,877 grafts; p ¼ 0.05) and (B) propensity-matched patients. LAD ¼ left
complications (particularly incisional infection), has
anterior descending coronary artery; other abbreviations as in Figure 3.
contributed to the very low use of multiarterial revascularization that we observed. We believe that our study findings have clear implications for the optimal
choice
of
procedure
for
a
substantial
divergent outcomes at 1 year (16). We believe that the
proportion of patients undergoing surgical revascu-
poorer patency of vein grafts demonstrated in
larization, and indicate that multiarterial revasculari-
our study may be a more important contributing
zation is greatly underused in contemporary practice.
factor in this analysis. We also confirmed an
STUDY
association between use of off-pump surgery and
mandatory, large clinical and administrative data-
under-revascularization, which we have previously
bases provides a unique opportunity to compare
STRENGTHS
AND
LIMITATIONS. Using
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Multiarterial Versus Single-Arterial CABG
surgical strategies in representative patient pop-
2247
F I G U R E 5 Cumulative Incidence Estimates for Percutaneous Reintervention After
ulations with long-term follow-up. This adds to the
CABG
data in randomized trials, which tend to evaluate Cumulative Probability of PCI Re-Intervention (%)
outcomes in highly selected patients, and surgical practice settings that differ from routine clinical practice. As indicated in the preceding text, this type of approach has several limitations. There are no data on the quality of distal coronary targets, which reduces the ability to fully adjust for variation between the patient groups. Patients undergoing singlearterial
CABG
were
very
different
from
those
selected for multiarterial CABG, and although multivariable Cox analysis and propensity matching accounted for differences in variables recorded in the dataset, the likelihood is that hidden confounding
15
10
5
0
variables may explain some of the study findings. Importantly, the way in which the data are recorded
Artery Native Vein
makes it difficult to accurately identify which target vessels received which conduits and, specifically, to
Arterial Graft vs. Vein Graft HR 0.08 (95% CI 0.03 to 0.2); Native Vessel vs. Vein Graft HR 5.5 (95% CI 4.9 to 6.8); Fine-Gray P ≤ 0.001
0
2
4 Years Since Surgery
6
8
4,532 14,553 13,957
3,628 11,083 11,058
2,433 7,212 7,391
1,232 3,602 3,709
609 1,770 1,865
identify the deployment of right internal mammary artery versus radial artery. Additionally, there were
Cumulative incidence estimates for percutaneous reintervention after coronary artery
no data for key post-operative variables, including
bypass grafting (CABG) to non-left anterior descending coronary artery territory, according to bypass conduit used, are shown. Time-to-event curves show the risk of
compliance with secondary prevention and angio-
percutaneous reintervention after coronary bypass surgery in non-left anterior
graphic follow-up after 2012. Finally, in our cohort,
descending territories, comparing native vessel versus arterial graft versus venous
clinical and angiographic follow-up was restricted to
graft. Significantly higher rates of reintervention are seen for venous bypass grafts
hospital visits in the state, potentially reducing the
(p < 0.001). PCI ¼ percutaneous coronary intervention; other abbreviations as in
applicability of our findings to other practice settings.
Figure 3.
CONCLUSIONS effectiveness of multiarterial versus single-arterial This study used data from a clinical registry of coro-
CABG. We found that single-arterial CABG, which
nary bypass surgery with linkage to mandatory state
was employed in 85% of patients, was associated with
claims
increased
records
to
evaluate
the
comparative
mortality,
myocardial
infarction,
and
T A B L E 3 30-Day and Long-Term Outcomes of Patients Undergoing Single Versus Multiple Arterial Revascularization
All Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
Propensity Matched
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
p Value
Mortality 30-day
1.2 (1.1–1.3)
1.2 (1.1–1.4)
0.8 (0.5–1.1)
0.01
0.6 (0.4–0.9)
0.8 (0.5–1.1)
0.40
4.4 (4.1–4.6)
4.7 (4.4–4.9)
2.5 (2.1–3.1)
<0.001
2.4 (2.0–3.0)
2.6 (2.1–3.2)
0.70
24.4 (23.9–24.9)
26.0 (25.4–26.5)
15.0 (13.8–16.1)
<0.001
17.3 (16.1–18.6)
15.1 (14.0–16.3)
0.01
0.2 (0.17–0.29)
0.2 (0.17–0.29)
0.2 (0.11–0.43)
0.90
0.3 (0.2–0.5)
0.2 (0.1–0.4)
0.50
3.6 (3.4–3.9)
3.6 (3.4–3.8)
3.9 (3.3–4.6)
0.40
4.2 (3.6–4.9)
3.9 (3.3–4.6)
0.50
11.4 (11.0–11.8)
11.4 (11.0–11.9)
11.5 (10.5–12.6)
0.80
13.5 (12.4–14.7)
11.5 (10.5–12.6)
0.02
0.3 (0.25–0.38)
0.3 (0.2–0.4)
0.3 (0.2–0.6)
0.80
0.4 (0.2–0.6)
0.3 (0.2–0.6)
0.70
1.7 (1.5–1.8)
1.7 (1.6–1.9)
1.4 (1.0–1.8)
0.10
1.9 (1.5–2.4)
1.4 (1.0–1.8)
0.06
8.3 (8.0–8.7)
8.6 (8.2–9.0)
6.7 (5.9–7.6)
<0.001
8.1 (7.2–9.1)
6.6 (5.8–7.4)
0.02
1-yr 10-yr Reintervention 30-day 1-yr 10-yr Myocardial infarction 30-day 1-yr 10-yr Deep sternal wound infection 30-day
0.5 (0.4–0.6)
0.5 (0.4–0.6)
0.5 (0.3–0.8)
0.60
0.4 (0.3–0.7)
0.6 (0.4–0.8)
0.50
1-yr
0.8 (0.7–0.9)
0.8 (0.7–0.9)
1.1 (0.8–1.5)
0.09
0.7 (0.5–1.1)
1.1 (0.8–1.5)
0.10
Values are % (95% confidence interval).
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Multiarterial Versus Single-Arterial CABG
NOVEMBER 5, 2019:2238–48
repeat revascularization overall compared with multiarterial CABG. Venous compared with arterial bypass grafts were associated with reduced freedom from reintervention. These findings suggest that multiarterial surgical revascularization is underused
PERSPECTIVES COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Multiarterial surgical
in contemporary clinical practice and highlight the
revascularization is associated with superior survival,
need for targeted referral of younger patients likely to
graft patency, and freedom from myocardial infarc-
benefit from a multiarterial surgical revascularization
tion and repeat intervention.
strategy.
TRANSLATIONAL OUTLOOK: Future studies should compare outcomes associated with various
ADDRESS
FOR
CORRESPONDENCE:
Dr.
Joanna
types of second conduits when the left internal
Chikwe, Department of Cardiac Surgery, Smidt Heart
mammary artery is employed in multivessel surgical
Institute, Cedars-Sinai Medical Center, 8700 Beverly
revascularization.
Boulevard, Los Angeles, California 90048. E-mail: [email protected]. Twitter: @CedarsSinai.
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2. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. J Am Coll Cardiol 2011;58:
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studies comparing bilateral versus single internal thoracic artery for coronary artery bypass grafting: a meta-analysis. J Am Heart Assoc 2018;7: e008010.
2584–614. 3. Taggart DP, Benedetto U, Gerry S, et al. Bilateral versus single internal-thoracic-artery grafts at 10 years. N Engl J Med 2019;380:437–46. 4. Gaudino M, Benedetto U, Fremes S, et al.
10. Rocha RV, Tam DY, Karkhanis R, et al. Multiple arterial grafting is associated with better outcomes for coronary artery bypass grafting patients. Circulation 2018;138:2081–90.
Radial artery versus saphenous vein in coronary artery bypass surgery. N Engl J Med 2018;378: 2069–77.
11. Devereaux PJ, Bhandari M, Clarke M, et al. Need for expertise based randomized controlled trials. BMJ 2005;330:88.
5. Desai ND, Cohen EA, Naylor CD, Fremes SE. A randomized comparison of radial-artery and saphenous-vein coronary bypass grafts. N Engl J Med 2004;351:2302–9.
12. Levin MA, Lin HM, Prabhaker G, McCormick PJ, Egorova NN. Alive or dead: validity of the Social Security Administration Death Master File after 2011. Health Serv Res 2019;54:24–33.
6. Myers WO, Berg R, Ray JF, et al. All-artery multigraft coronary artery bypass grafting with only internal thoracic arteries possible and safe: a randomized trial. Surgery 2000;128: 650–9. 7. Nasso G, Coppola R, Bonifazi R, et al. Arterial revascularization in primary coronary artery bypass grafting: direct comparison of 4 strategies – results of the Stand-in Y Mammary study. J Thorac Cardiovasc Surg 2009;137:1093–100.
17. Chikwe J, Lee T, Itagaki S, et al. Long-term outcomes after off-pump versus on-pump coronary artery bypass grafting by experienced surgeons. J Am Coll Cardiol 2018;72:1478–86. 18. Aldea GS, Bakaeen F, Pal J, et al., Society of Thoracic Surgeons. The Society of Thoracic Surgeons Clinical Practice Guidelines on arterial conduits for coronary artery bypass grafting. Ann Thorac Surg 2016;101:801–9. 19. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society for CardioThoracic Surgery (EACTS). Eur Heart J 2014;35: 2541–619.
13. Cox DR. Regression models and life-tables. J Roy Statist Soc Ser B 1972;34:187–220. 14. Wei LY, Lin DY, Weissfeld L. Regression analysis of multivariate incomplete failure time data by modeling marginal distribution. J Amer Statist
KEY WORDS arterial graft, coronary revascularization, off-pump coronary bypass surgery, on-pump coronary bypass surgery
Assoc 1989;84:1065–73. 15. Roseunbaum PR, Rubin DB. The central role of the propensity score in observational studies for
A PPE NDI X For supplemental figures and tables, please see the online version of this
causal effects. Biometrika 1983;70:41–55.
paper.
VOL. 74, NO. 18, 2019
ª 2019 PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
Outcomes of Second Arterial Conduits in Patients Undergoing Multivessel Coronary Artery Bypass Graft Surgery Joanna Chikwe, MD,a,b Erick Sun, BA,a Edward L. Hannan, PHD,c Shinobu Itagaki, MD, MSC,a Timothy Lee, MD,a David H. Adams, MD,a Natalia N. Egorova, PHDd
ABSTRACT BACKGROUND Benefits of multiarterial versus single-arterial coronary bypass grafting (CABG) are debated. OBJECTIVES This study sought to compare long-term survival, morbidity, and graft patency after multiarterial versus single-arterial CABG. METHODS Mandatory clinical registries linked with discharge databases were used to identify baseline and operative characteristics and outcomes of 42,714 patients undergoing CABG from 2005 through 2012. Patients with single-vessel disease, without arterial conduits, or undergoing emergency, reoperative, or concomitant procedures were excluded. Survival, stroke, myocardial infarction, and repeat revascularization rates were compared using Cox modeling, and patients were matched by propensity score. Median follow-up was 7.8 years (interquartile range: 5 to 10 years); last follow-up was December 31, 2016. RESULTS Of the 26,124 patients, 3,647 (14.0%) underwent multiarterial CABG. Single-arterial CABG patients were older (mean 68 vs. 61 years; p < 0.001), had more comorbidities, and received fewer bypass grafts (3.4 vs. 3.6; p < 0.001). After adjusting for baseline differences, multiarterial CABG was associated with lower 10-year mortality compared with single-arterial CABG in 3,588 propensity-matched pairs (15.1% vs. 17.3%; p ¼ 0.01). Multiarterial CABG was associated with lower 10-year myocardial infarction (hazard ratio: 0.81; 95% confidence interval: 0.69 to 0.95) and lower 10-year reintervention rate (hazard ratio: 0.81; 95% confidence interval: 0.67 to 0.99). CONCLUSIONS In contemporary practice, single-arterial CABG is used in 85% of patients and is associated with increased long-term mortality, myocardial infarction, and reintervention compared with multiarterial CABG. Multiarterial CABG is underused in contemporary surgical revascularization, and targeted referral of younger patients for multiarterial revascularization may address this practice gap. (J Am Coll Cardiol 2019;74:2238–48) © 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.
A
rterial coronary bypass grafts have long been
compared in randomized clinical trials, which showed
associated with superior patency and sur-
no incremental survival benefit in intention-to-treat
vival compared with venous bypass grafts
analysis (3–7). Randomization is the only way to con-
alone in patients undergoing coronary artery bypass
trol for unmeasured confounding variables and selec-
graft (CABG) surgery (1,2). Outcomes of single-
tion bias, but such trials require many years to
arterial
generate adequate follow-up, involve highly selected
versus
multiarterial
CABG
have
been
Listen to this manuscript’s audio summary by Editor-in-Chief
From the aDepartment of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, New York, New York; bDepartment of
Dr. Valentin Fuster on
Surgery, The State University of New York, Stony Brook, New York; cSchool of Public Health, University at Albany, State University
JACC.org.
of New York, Albany, New York; and the dDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. The Icahn School of Medicine at Mount Sinai receives royalty payments for intellectual property from Edwards Lifesciences rand Medtronic. Dr. Chikwe has received speaker honoraria from Edwards Lifesciences. Dr. Adams has been a coprincipal investigator for trials for Medtronic and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Bernard J. Gersh, MB, ChB, DPhil, served as Guest Associate Editor for this paper. Manuscript received July 15, 2019; revised manuscript received August 13, 2019, accepted August 14, 2019.
ISSN 0735-1097/$36.00
https://doi.org/10.1016/j.jacc.2019.08.1043
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2239
patients and surgeons, and are commonly underpow-
missing personal or surgeon identifiers and
ABBREVIATIONS
ered to detect important clinical differences (8,9).
patients from out of state were excluded. The
AND ACRONYMS
Analysis of clinical registries can yield additional
Open Heart Surgery Registry was used to
relevant information, such as longer-term outcomes
identify baseline characteristics, the number
in much larger populations more representative of
of arterial and venous conduits, and incom-
clinical practice, with sufficient power to permit sub-
plete revascularization, which was defined as
group analysis of specific patient populations and
more diseased territories than the number of
practice patterns
grafts placed (Online Table 2).
(10,11). Our objective was to
CABG = coronary artery bypass grafting
CI = confidence interval HR = hazard ratio LAD = left anterior descending coronary artery
compare the long-term clinical and angiographic out-
SURGEON CRITERIA. We performed a sub-
comes of single-arterial and multiarterial CABG in
PCI = percutaneous coronary
group analysis to reduce the effect of surgeon
intervention
contemporary clinical practice.
expertise on outcomes. This involved applying
METHODS
surgeon-specific case volume thresholds similar to those used in randomized controlled trials and
STUDY DESIGN. This retrospective cohort analysis
observational studies (8,12). In this subgroup anal-
compared outcomes of patients with multivessel
ysis, patients were excluded if their surgeon had
coronary disease receiving single-arterial versus
performed <100 CABG procedures before the index
multiarterial CABG between January 1, 2005, and
CABG procedure. A total of 76 of 97 surgeons per-
December 31, 2012, in New Jersey. Patients were fol-
forming single-arterial, and 31 of 97 surgeons per-
lowed up to December 31, 2016. The study was
forming
approved by institutional review boards at the New
volume threshold for this analysis. The median
Jersey Department of Health and the authors’ in-
number of CABGs completed in the last 365 days by
stitutions, including a waiver of informed consent.
these surgeons at the time of the index procedure was
REGISTRIES. A clinical database, the mandatory state
Open Heart Surgery Registry, was used to identify patients, baseline clinical characteristics, and opera-
multiarterial
CABG
met
the
minimum
91 for single-arterial CABG, and 34 for multiarterial CABG, respectively. SEE PAGE 2249
tive variables. Under the oversight of the Department of Health, data on every individual patient undergo-
STUDY ENDPOINTS. The primary endpoint was all-
ing cardiac surgery are collected by clinical staff at all
cause mortality, identified from 4 separate sources,
hospitals performing cardiac surgery in the state. In-
including the New Jersey Vital Statistics death regis-
dividual charts are sampled to audit the quality of
try, and discharge disposition on the Open Heart
data collection quarterly, and external medical audi-
Registry, the Cardiac Catheterization Registry, and
tors verify data annually.
the New Jersey Discharge Data Collection System.
Long-term clinical outcome and graft patency data
There was near 100% agreement in deaths identified,
were obtained for individual patients by linking this
and for the few discrepant dates, the earliest date of
clinical registry with 3 Department of Health manda-
death reported was used. The date of last follow-up
tory databases using deterministic matching with a
was December 31, 2016, for all outcomes, except for
98% success rate. These were the New Jersey Cardiac
cardiac catheterizations, where the last available
Catheterization Registry, the New Jersey Discharge
follow-up was December 31, 2012. Secondary out-
Data Collection System (an administrative database
comes included stroke, myocardial infarction, repeat
containing data on all inpatient episodes from 1994
revascularization, and graft patency. Stroke was
and outpatient visits from 2004), and the New Jersey
defined as permanent neurological deficit due to an
Vital Statistics deaths registry, which contains all
ischemic or hemorrhagic cerebrovascular event, not
deaths known to any state or federal agency for New
including transient ischemic attacks. Repeat revas-
Jersey residents. Online Table 1 provides additional
cularization was defined as a post-operative redo
details.
CABG or percutaneous coronary intervention (PCI).
STUDY POPULATION. All patients undergoing iso-
lated multivessel CABG were included. Exclusion criteria were concomitant or previous cardiac surgery, hemodynamic instability (pre-operative shock, cardiopulmonary resuscitation, or inotrope require-
Native vessel and bypass conduit patency was determined by identifying patients with reports of stenosis >50% in any coronary angiography performed after the index CABG operation, through linkage with the New Jersey Cardiac Catheterization Registry.
ment), emergency status, and no arterial conduit use.
STATISTICAL ANALYSIS. Continuous variables are
In order to ensure complete follow-up, patients with
reported as mean SD. Categorical variables are
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F I G U R E 1 Patient Selection Flow Diagram
Initial Cohort • all patients who underwent CABG from 2005-2012 in New Jersey State n = 42,714
Exclusion Criteria: • single bypass graft (n = 4,891) • no arterial graft (n = 5,581) • no internal mammary artery graft (n = 778) • emergency status (n = 1,589) • hemodynamic instability (n = 924) • concomitant cardiac surgery (n = 9,921) • previous cardiac surgery (n = 1,329) • missing data (n = 299)
Final Total Cohort n = 26,124
Multi-Arterial Revascularization n = 3,647 (14.0%)
Single Arterial Revascularization n = 22,477 (86.0%)
CONSORT style diagram showing study patient cohort according to inclusion and exclusion criteria. CABG ¼ coronary artery bypass grafting.
expressed as proportions. Baseline characteristics
outcome, multiarterial revascularization was incor-
were compared using Student’s t-test for normally
porated as a dichotomous variable (13,14). Covariates
distributed continuous variables, Wilcoxon’s rank
adjusted for included patient age, sex, race, payer,
sum test for non-normally distributed continuous
year of surgery, body mass index, renal dysfunction,
variables, and Pearson’s chi-square test for categori-
pulmonary disease, hepatic dysfunction, prior or
cal
current
variables.
Comparisons
between
propensity-
malignancy;
cardiovascular
risk
factors
matched groups were performed with standardized
including diabetes, smoking, history of cerebrovas-
differences, paired Student’s t-test, and McNemar’s
cular disease including prior stroke, peripheral
chi-square test.
vascular disease, congestive heart failure, hyperten-
Kaplan-Meier analysis was used to estimate prob-
sion, atrial fibrillation, previous myocardial infarc-
ability of survival, and comparisons were performed
tion, previous PCI, left ventricular ejection fraction,
with the log-rank test (Online Figure 1). Competing
left main stem stenosis, number of diseased vessels,
risk analysis was used to estimate cumulative event
number of total anastomoses, use of cardiopulmo-
rates for myocardial infarction, stroke, repeat revas-
nary
cularization, and graft patency with the competing
beta-blockers, aspirin, statins, glycoprotein IIb/IIIa
event of death. Comparisons were performed with
inhibitors, adenosine diphosphate inhibitors, and
the Fine-Gray test. Hazard ratios (HR) were obtained
warfarin (see Online Table 1 for definitions). We
using Cox proportional hazard models. Given the
controlled for clustering of patients by surgeon and
possibility of repeated events for revascularization
hospital using a marginal Cox approach with a robust
when patients had multiple grafts, we performed
sandwich variance estimator. Additionally, individ-
bypass;
and
the
use
of
pre-operative
additional analysis using the Anderson-Gill model to
ual surgeon case volume was adjusted for, first, by
analyze risk of recurrent revascularization. For each
including annual volume as a covariate in the
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Multiarterial Versus Single-Arterial CABG
T A B L E 1 Baseline Characteristics of Patients Undergoing Single- Versus Multiple-Arterial Revascularization
All
Propensity Matched
Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
66.7 10.6
67.6 10.3
75.7
74.3
34.2 8.2
Hypertension Diabetes mellitus
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
Standardized Difference (%) p Value
60.8 10.5
<0.001
61.1 10.2
60.9 10.4
1.7
85.0
<0.001
85.0
84.8
0.7
0.7
34.2 8.2
34.4 8.7
0.1
34.5 8.2
34.4 8.8
1.2
0.6
92.4
93.0
89.0
<0.001
90.1
89.3
2.6
0.3
47.0
48.1
40.3
<0.001
40.3
40.6
0.7
0.8 0.9
Demographics Age, yrs Male BMI, kg/m2
0.5
Comorbidities
Peripheral vascular disease
17.0
17.5
13.8
<0.001
13.9
13.9
0.07
Tobacco use
63.5
63.7
61.7
0.02
62.1
61.7
0.8
0.7
Atrial fibrillation
28.4
29.5
21.4
<0.001
21.3
21.6
0.7
0.8
Heart failure
26.4
27.7
18.8
<0.001
18.9
19.0
0.4
0.9
Previous MI
47.4
47.9
43.7
<0.001
44.0
43.8
0.5
0.8
Previous PCI
24.4
24.4
24.1
0.7
23.9
24.3
0.9
0.7
Cerebrovascular accident
8.0
8.4
5.9
<0.001
6.0
6.0
0.0
0.9
COPD
25.1
25.7
21.5
<0.001
21.9
21.7
0.3
0.9
Renal failure (Cr >2.3 mg/dl)
3.4
3.8
1.4
<0.001
1.6
1.5
1.2
0.5
Dialysis
2.3
2.5
1.0
<0.001
1.1
1.1
0.6
0.7
Liver disease
2.1
2.2
1.6
0.02
1.7
1.6
0.6
0.8
Cancer
7.2
7.6
4.6
<0.001
5.1
4.7
1.9
0.4
49.8 12.2
49.6 12.4
51.0 10.9
<0.001
50.6 11.6
50.9 11.0
0.7
0.3
11.3
11.9
8.0
<0.001
8.8
8.1
0.7
0.4
35%–50%
43.7
43.9
42.7
43.3
42.8
0.06
>50%
44.9
44.2
49.4
47.9
49.1
0.4
2.5 0.9
2.5 0.9
2.5 0.8
0.7
2.5 0.8
2.5 0.8
0.6
0.8
I
11.8
11.9
11.0
0.3
10.3
11.1
1.1
0.7
II
36.9
36.8
37.4
38.4
37.5
1.6
III
38.7
38.6
39.5
39.4
39.4
2.2
IV
12.6
12.7
12.1
11.9
12.0
1.9
38.9
39.4
0.2
61.1
60.7
0.2
Pre-operative condition Ejection fraction <35%
NYHA functional class
Status Elective
35.0
34.2
39.3
Urgent
65.0
65.8
60.7
<0.001
0.7
Values are mean SD or %, unless otherwise indicated. BMI ¼ body mass index; COPD ¼ chronic obstructive pulmonary disease; Cr ¼ creatinine; MI ¼ myocardial infarction; NYHA ¼ New York Heart Association; PCI ¼ percutaneous coronary intervention.
models, and second, by performing a subgroup
on
analysis within which inclusion criteria included a
matched cohort, we fit a Cox model for mortality,
long-term
mortality
among
the
propensity-
minimum threshold individual surgeon case volume
adjusting for all measured covariates and controlling
of 100 of the index-case type.
for patients clustered within matched pairs (15,16).
Propensity score matching was used to compare
Besides a subgroup analysis based on surgeon vol-
mortality and secondary endpoints in single-arterial
ume, a number of subgroup analyses were per-
and multiarterial patients with similar characteris-
formed on the basis of age, ejection fraction, and the
tics (14,15). Propensity score was calculated using
type of the second arterial conduit (radial vs. inter-
logistic regression fit for multivessel CABG, adjust-
nal mammary artery), and comparing patients un-
ing for all measured covariates, with patients clus-
dergoing
tered within hospital. The C-statistic for the model
revascularization (Online Tables 3 to 5 and Online
single-arterial
versus
total-arterial
was 0.78. Matching was performed one-to-one with
Figures 2 to 6).
a caliper width of 0.10 of logit of the propensity
All tests were 2-tailed, and an alpha level of 0.05
score. To quantify the effect of multiarterial CABG
was considered statistically significant. All statistical
2241
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Multiarterial Versus Single-Arterial CABG
NOVEMBER 5, 2019:2238–48
T A B L E 2 Operative Characteristics of Patients Undergoing Single Versus Multiple Arterial Revascularization
All
Left main disease
Propensity Matched
Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
36.8
37.2
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
Standardized Difference (%)
p Value
34.2
<0.001
34.8
34.2
0.8
0.6
Vessel disease 2.8 0.4
2.8 0.4
2.8 0.4
0.2
2.8 0.4
2.8 0.4
0.8
0.6
2-vessel disease
17.8
17.9
17.0
0.2
17.5
17.1
0.8
0.6
3-vessel disease
82.2
82.1
83.0
82.5
92.9
0.8
Total diseased vessels
Vessel disease by pre-operative angiographic data 2.7 0.5
2.7 0.5
2.7 0.5
0.9
2.7 0.6
2.7 0.6
1.7
0.6
2-vessel disease
22.4
22.4
22.3
0.9
22.1
22.4
3.1
0.7
3-vessel disease
76.0
75.9
76.0
75.8
75.9
2.7
3.4 0.9
3.4 0.9
3.6 1.0
<0.001
3.6 1.0
3.6 1.0
3.4
1.2 0.5
1.0 0
2.3 0.6
<0.001
1.0 0
2.3 0.6
Total diseased vessels
Total anastomoses Arterial
0.4 <0.001
IMA
1.1 0.4
1.0 0.03
1.8 0.7
<0.001
1.0 0.02
1.8 0.7
<0.001
Radial
0.1 0.3
0.001 0.04
0.5 0.6
<0.001
0.003 0.06
0.5 0.6
<0.001
2.2 1.0
2.4 0.9
1.3 1.0
<0.001
2.6 1.0
1.3 1.0
Incomplete revascularization
7.9
8.1
6.9
0.01
7.8
6.9
2.5
0.2
On-pump CABG
71.5
75.1
49.5
<0.001
49.4
50.2
2.7
0.5
107 55
107 55
106 56
0.4
106 56
106 56
2.4
0.8
Venous
Surgeon volume/year
<0.001
Values are % or mean SD, unless otherwise indicated. CABG ¼ coronary artery bypass grafting; IMA ¼ internal mammary artery.
analyses were performed using SAS version 9.4 (SAS
the number of bypass grafts performed was signifi-
Institute, Cary, North Carolina).
cantly higher, and the rate of incomplete revascularization
RESULTS
was
lower
in
patients
undergoing
multiarterial revascularization (Table 2). The individual mean annual surgeon volume during the
PATIENTS. The overall study cohort included 42,714
study period was 107 CABG operations and was not
patients who underwent CABG between January 1,
significantly different for single-arterial versus mul-
2005, and December 31, 2012. After excluding patients
tiarterial CABG patients (Figure 2). Propensity score
undergoing single-vessel bypass (n ¼ 4,891, 11.5%),
matching produced 3,588 matched patient pairs,
vein grafts only (n ¼ 5,581, 13.1%), no use of an in-
with standardized differences <5% for all baseline
ternal mammary artery conduit (n ¼ 778, 1.8%),
variables (Table 1).
emergency surgery (n ¼ 1,589, 3.7%), hemodynamic
SURVIVAL. In the overall cohort, multiarterial CABG
instability (n ¼ 924, 2.2%), concomitant surgery
was associated with lower mortality at 10 years
including any valve, aortic, or vascular procedure
compared with single-arterial CABG (15.0% vs. 26.0%;
(n
¼
9,921,
23.2%),
previous
cardiac
surgery
adjusted HR: 0.84; 95% confidence interval [CI]: 0.76
(n ¼ 1,329, 3.1%), and patients with missing data
to 0.92; p < 0.001) (Online Figure 1). Multiarterial
(n ¼ 299, 0.7%), 26,124 patients remained, consisting
CABG was associated with lower 10-year mortality
of 22,477 (86.0%) single-arterial and 3,647 (14.0%)
compared
multiarterial CABG patients (Figure 1).
propensity-matched pairs (15.1% vs. 17.3%; p ¼ 0.01)
Table 1 shows selected characteristics of the study patients
(all
variables
are
provided
in
with
single-arterial
CABG
in
3,588
(Central Illustration). There were 15,697 patients #70
Online
years of age (12,752 single-arterial revascularization,
Table 2). There were substantial differences in
2,945 multiarterial revascularization; 2,886 propensity-
baseline patient characteristics: multiarterial CABG
matched pairs) and 10,427 patients >70 years of age
patients were on average 7 years younger, much
(9,725 single-arterial revascularization, 702 multi-
more likely to be male, and with much less comor-
arterial revascularization; 688 propensity-matched
bidity, including significantly lower rates of dia-
pairs). When patients were stratified by age, multi-
betes, peripheral vascular disease, heart failure, and
arterial CABG was associated with lower 10-year
prior myocardial infarction (Table 1). Additionally,
mortality compared with single arterial CABG in
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Multiarterial Versus Single-Arterial CABG
Rate of Multi-Arterial Revascularization by Surgeon (%)
F I G U R E 2 Rates of Multiarterial Revascularization by Individual Surgeon Annual Case Volume
100 90 80 70 60 50 40 30 20 10 0 0
50
150
100 Surgeon CABG Volume/Year
95% Confidence Limits
95% Prediction Limits
Individual surgeon rates of multiarterial revascularization in New Jersey between 2005 and 2012, showing very wide practice variation, and no significant relationship between surgeon case volume and rates of multiarterial revascularization. Individual dots represent individual surgeon’s annual case volume. Lines represent 95% confidence limits. CABG ¼ coronary artery bypass grafting.
patients #70 years of age (adjusted HR: 0.87; 95% CI:
0.98; p ¼ 0.01) at 10 years in the overall cohort, and in
0.77 to 0.99), but not in patients >70 years of age
the propensity-matched cohort (6.6% vs. 8.1%;
(adjusted HR: 0.91; 95% CI: 0.75 to 1.1). The survival
p ¼ 0.02) (Figure 3A and Online Figure 2). Likewise,
benefit was similar in subgroup analysis based on
the rate of repeat revascularization was significantly
individual surgeon volume $100 index cases, which
lower in the propensity-matched cohort (11.5% vs.
single-arterial,
13.5%; HR: 0.86; 95% CI: 0.75 to 0.98; p ¼ 0.02)
2,931 multiarterial; 2,887 propensity-matched pairs)
(Figure 3B and Online Figure 3). The rate of stroke was
(adjusted
included
24,992
patients
(21,991
0.95;
significantly lower (4.1% vs. 6.4%; p < 0.001) in
p ¼ 0.005), but was not significant when restricted
multiarterial versus single-arterial CABG in the over-
only to patients with ejection fraction #30% (n ¼
all cohort but did not reach statistical significance in
2,777:
propensity-matched
HR:
2,513
0.83;
single
95%
arterial,
CI:
0.73
264
to
multiarterial;
262 propensity-matched pairs) (adjusted HR: 0.95; 95% CI: 0.68 to 1.3; p ¼ 0.80) (Online Figure 7).
patients
(4.2%
vs.
5.1%;
p ¼ 0.06) (Figure 3C and Online Figure 3). In a subgroup analysis of symptom-driven postoperative angiography, we compared patients with
SECONDARY OUTCOMES. The incidence of myocar-
single- versus total-arterial revascularization because
dial infarction was significantly lower after multi-
this was the only way to reliably ensure we were
arterial CABG compared with single-arterial CABG
comparing artery versus vein for the non-left anterior
(6.7% vs. 8.6%; adjusted HR: 0.85; 95% CI: 0.73 to
descending coronary artery (LAD) conduit. In this
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Multiarterial Versus Single-Arterial CABG
NOVEMBER 5, 2019:2238–48
C E N T R A L IL L U ST R A T I O N Long-Term Mortality After Multiarterial Versus Single-Arterial Coronary Artery Bypass Grafting
35
HR 0.80 (95% CI 0.72 to 0.90) Fine-Gray p = 0.006
30 Mortality Probability (%)
2244
25 20 15 10 5 0
Multi-Arterial Single-Arterial
0
2
4
6 8 Years Since Surgery
3,588 3,588
3,459 3,437
3,339 3,317
2,655 2,646
1,745 1,706
10
12
867 822
427 412
Chikwe, J. et al. J Am Coll Cardiol. 2019;74(18):2238–48.
Long-term mortality is shown after multiarterial versus single-arterial coronary artery bypass grafting in 3,588 propensity-matched patient pairs. A significant survival benefit with multiarterial revascularization at 12 years (p ¼ 0.006) is shown. CI ¼ confidence interval; HR ¼ hazard ratio.
subgroup analysis, there were 215 non-LAD grafts
indicates that these groups were well matched
overall (140 internal mammary, and 75 radial arteries)
for differences in baseline characteristics and that
and 211 non-LAD grafts after propensity matching (139
the impact of unmeasured covariates was not
internal mammary and 72 radial arteries). The time to
substantial.
>50% stenosis in non-LAD grafts was shorter in single-arterial CABG compared with total-arterial
DISCUSSION
CABG patients in the overall cohort (adjusted HR: 0.89; 95% CI: 0.68 to 1.2; p ¼ 0.06) (Figure 4). When
In a contemporary multicenter cohort of patients
evaluating non-LAD grafts only, the rate of repeat PCI
undergoing CABG, which included long-term clinical
was significantly lower in arterial grafts (adjusted HR
and angiographic follow-up, the long-term risks of
of arterial graft vs. venous graft: 0.08; 95% CI: 0.03 to
myocardial infarction and death associated with
0.2; p < 0.001) and significantly higher in native
single-arterial CABG were higher than those associ-
vessels (adjusted HR of native vessel vs. venous graft:
ated with multiarterial CABG. Venous bypass grafts
5.5; 95% CI: 4.5 to 6.8; p < 0.001 in the overall cohort
exhibiting >50% stenosis were more likely to undergo
and in propensity-matched patients) (Figure 5).
repeat revascularization via percutaneous interven-
The 30-day mortality and major complications are
tion in symptom-guided post-operative angiographic
shown in Table 3: the lack of significant difference
follow-up than arterial conduits. Single-arterial CABG
between
was also associated with increased rates of repeat
propensity-matched
treatment
groups
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Multiarterial Versus Single-Arterial CABG
2245
F I G U R E 3 Cumulative Incidence of Secondary Outcomes in Propensity-Matched Patients
Cumulative Probability of Myocardial Infarction (%)
20
Cumulative Probability of Re-Intervention (%)
B
A
Adjusted Cox HR 0.81 (95% CI 0.69 to 0.95) Fine-Gray P = 0.02
15
10
5
0 0 Multi-Arterial Single-Arterial
3,588 3,588
2
4
3,389 3,356
6
8
10
Years Since Surgery 3,234 2,543 1,651 3,198 2,518 1,598
20
Adjusted Cox HR 0.86 (95% CI 0.75 to 0.98) Fine-Gray P = 0.02
15
10
5
0
820 755
2
0
12 Multi-Arterial Single-Arterial
405 375
3,588 3,588
4
6
8
Years Since Surgery 3,068 2,385 1,539 3,014 2,355 1,482
3,270 3,230
10
12
764 709
374 347
C Cumulative Probability of Stroke (%)
15
Adjusted Cox HR 0.81 (95% CI 0.64 to 1.0) Fine-Gray P = 0.07
10
5
0 0 Multi-Arterial Single-Arterial
3,588 3,588
2
4
3,425 3,396
6
8
Years Since Surgery 3,283 2,593 1,686 3,237 2,571 1,645 Multi-Arterial
10
12
832 788
410 392
Single-Arterial
Time-to-event curves showing cumulative incidence of (A) myocardial infarction, (B) repeat revascularization, and (C) stroke in propensity-matched patients undergoing single-arterial versus multiarterial coronary artery bypass grafting, with significantly higher rates of myocardial infarction (p ¼ 0.02) and repeat revascularization (p ¼ 0.02) in patients who underwent single compared with multiarterial revascularization. CI ¼ confidence interval; HR ¼ hazard ratio.
revascularization, including both repeat CABG and
single-arterial CABG was used in patients who tended
PCI, compared with multiarterial revascularization.
to be older with more comorbidity, and the technique
Our findings provide data that supplement the
was also associated with fewer grafts and increased
findings of prior comparative studies. These include
risk of incomplete revascularization. To the best of
>100 observational analyses, most of which have
our knowledge, our analysis is one of the first to
suggested
adjust
a
survival
benefit
from
multiarterial
for
all
these
factors
including
using
revascularization, and several randomized controlled
pre-operative angiographic data to account for dif-
studies that showed no benefit in intention-to-treat
ferences in completeness of revascularization. The
analysis (2–8,10,11). The major limitation of observa-
lack of a significant difference in major post-operative
tional studies are confounding variables arising from
morbidity at 30 days indicates that the impact of
selection bias, which cannot be completely adjusted
hidden confounders is likely to be very small. It has
for in a retrospective analysis (16). In our cohort,
been suggested that hidden confounders may explain
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NOVEMBER 5, 2019:2238–48
linked to reduced long-term survival in an over-
F I G U R E 4 Cumulative Incidence Estimates for Detection of 50% Stenosis
lapping study cohort (17). There has been 1 large, multicenter, randomized
A Cumulative Probability of 50% Non-LAD Re-Stenosis (%)
50
study and a meta-analysis of randomized trials
Adjusted Cox HR 0.89 (95% CI 0.68 to 1.2) Fine-Gray P = 0.06
comparing single-arterial with multiarterial CABG (3,4). These trials have not typically been powered to
40
detect differences in mortality rate; instead, they have been based on composite outcomes including
30
death, myocardial infarction, and repeat revascularization. For example, ART (Arterial Revascularisation
20
Trial), a large randomized trial comparing outcomes of bilateral and single internal mammary artery, re-
10
ported 10-year mortality of 20.3% in the multiarterial group and 21.2% in the single-arterial CABG group
0
Single-Arterial (Vein Graft) Total-Arterial (Arterial Graft)
(p ¼ 0.62) (3). It would have required >20,000 pa-
0
2
4 Years Since Surgery
6
8
6,662
5,192
3,583
1,640
743
ence with an a of 0.05. The negative findings of the
215
170
135
82
44
ART trial have been attributed to the high rate of
tients to have an 80% power of detecting this differ-
crossover (13.9%) from bilateral to single internal
B Cumulative Probability of 50% Non-LAD Re-Stenosis (%)
50
mammary artery and the use of an additional arterial
HR 0.69 (95% CI 0.38 to 1.2) Fine-Gray P = 0.2
graft in 21.8% of the single internal mammary artery patients (8–10). Additionally, surgeon experience
40
may be a potential confounding variable, with lower experience associated with reduced use of and worse
30
outcomes with multiarterial revascularization. Our current study was designed to minimize the impact of
20
these limitations. Despite an abundance of high-quality data that
10
have helped define the patients who benefit from surgical revascularization with left internal mammary
0
to LAD anastomosis, the optimal surgical strategy for
0
2
4 Years Since Surgery
6
8
Single-Arterial (Vein Graft)
264
224
167
76
39
Observational and experimental data support use of a
Total-Arterial (Arterial Graft)
211
167
132
79
44
second arterial conduit, but the limitations of these
Single-Arterial (Vein Graft)
other coronary territories remains controversial.
Total-Arterial (Arterial Graft)
analyses are well recognized, and given the equivocal findings of randomized studies, consensus guidelines
Cumulative incidence estimates for detection of 50% stenosis are based on post-
place the lowest recommendations for use of multi-
operative angiographic follow-up in single versus total-arterial coronary bypass surgery.
arterial
Time-to-event curves showing competing risk of development of 50% stenosis in non-
compelling data and guidelines, combined with the
left anterior descending coronary artery bypass grafts in single versus total arterial revascularization patients with post-operative angiographic follow-up in (A) all pa-
revascularization
(18,19).
This
lack
of
incremental technical considerations and associated
tients (n ¼ 6,877 grafts; p ¼ 0.05) and (B) propensity-matched patients. LAD ¼ left
complications (particularly incisional infection), has
anterior descending coronary artery; other abbreviations as in Figure 3.
contributed to the very low use of multiarterial revascularization that we observed. We believe that our study findings have clear implications for the optimal
choice
of
procedure
for
a
substantial
divergent outcomes at 1 year (16). We believe that the
proportion of patients undergoing surgical revascu-
poorer patency of vein grafts demonstrated in
larization, and indicate that multiarterial revasculari-
our study may be a more important contributing
zation is greatly underused in contemporary practice.
factor in this analysis. We also confirmed an
STUDY
association between use of off-pump surgery and
mandatory, large clinical and administrative data-
under-revascularization, which we have previously
bases provides a unique opportunity to compare
STRENGTHS
AND
LIMITATIONS. Using
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Multiarterial Versus Single-Arterial CABG
surgical strategies in representative patient pop-
2247
F I G U R E 5 Cumulative Incidence Estimates for Percutaneous Reintervention After
ulations with long-term follow-up. This adds to the
CABG
data in randomized trials, which tend to evaluate Cumulative Probability of PCI Re-Intervention (%)
outcomes in highly selected patients, and surgical practice settings that differ from routine clinical practice. As indicated in the preceding text, this type of approach has several limitations. There are no data on the quality of distal coronary targets, which reduces the ability to fully adjust for variation between the patient groups. Patients undergoing singlearterial
CABG
were
very
different
from
those
selected for multiarterial CABG, and although multivariable Cox analysis and propensity matching accounted for differences in variables recorded in the dataset, the likelihood is that hidden confounding
15
10
5
0
variables may explain some of the study findings. Importantly, the way in which the data are recorded
Artery Native Vein
makes it difficult to accurately identify which target vessels received which conduits and, specifically, to
Arterial Graft vs. Vein Graft HR 0.08 (95% CI 0.03 to 0.2); Native Vessel vs. Vein Graft HR 5.5 (95% CI 4.9 to 6.8); Fine-Gray P ≤ 0.001
0
2
4 Years Since Surgery
6
8
4,532 14,553 13,957
3,628 11,083 11,058
2,433 7,212 7,391
1,232 3,602 3,709
609 1,770 1,865
identify the deployment of right internal mammary artery versus radial artery. Additionally, there were
Cumulative incidence estimates for percutaneous reintervention after coronary artery
no data for key post-operative variables, including
bypass grafting (CABG) to non-left anterior descending coronary artery territory, according to bypass conduit used, are shown. Time-to-event curves show the risk of
compliance with secondary prevention and angio-
percutaneous reintervention after coronary bypass surgery in non-left anterior
graphic follow-up after 2012. Finally, in our cohort,
descending territories, comparing native vessel versus arterial graft versus venous
clinical and angiographic follow-up was restricted to
graft. Significantly higher rates of reintervention are seen for venous bypass grafts
hospital visits in the state, potentially reducing the
(p < 0.001). PCI ¼ percutaneous coronary intervention; other abbreviations as in
applicability of our findings to other practice settings.
Figure 3.
CONCLUSIONS effectiveness of multiarterial versus single-arterial This study used data from a clinical registry of coro-
CABG. We found that single-arterial CABG, which
nary bypass surgery with linkage to mandatory state
was employed in 85% of patients, was associated with
claims
increased
records
to
evaluate
the
comparative
mortality,
myocardial
infarction,
and
T A B L E 3 30-Day and Long-Term Outcomes of Patients Undergoing Single Versus Multiple Arterial Revascularization
All Overall (N ¼ 26,124)
Single Arterial (n ¼ 22,477)
Multiarterial (n ¼ 3,647)
Propensity Matched
p Value
Single Arterial (n ¼ 3,588)
Multiarterial (n ¼ 3,588)
p Value
Mortality 30-day
1.2 (1.1–1.3)
1.2 (1.1–1.4)
0.8 (0.5–1.1)
0.01
0.6 (0.4–0.9)
0.8 (0.5–1.1)
0.40
4.4 (4.1–4.6)
4.7 (4.4–4.9)
2.5 (2.1–3.1)
<0.001
2.4 (2.0–3.0)
2.6 (2.1–3.2)
0.70
24.4 (23.9–24.9)
26.0 (25.4–26.5)
15.0 (13.8–16.1)
<0.001
17.3 (16.1–18.6)
15.1 (14.0–16.3)
0.01
0.2 (0.17–0.29)
0.2 (0.17–0.29)
0.2 (0.11–0.43)
0.90
0.3 (0.2–0.5)
0.2 (0.1–0.4)
0.50
3.6 (3.4–3.9)
3.6 (3.4–3.8)
3.9 (3.3–4.6)
0.40
4.2 (3.6–4.9)
3.9 (3.3–4.6)
0.50
11.4 (11.0–11.8)
11.4 (11.0–11.9)
11.5 (10.5–12.6)
0.80
13.5 (12.4–14.7)
11.5 (10.5–12.6)
0.02
0.3 (0.25–0.38)
0.3 (0.2–0.4)
0.3 (0.2–0.6)
0.80
0.4 (0.2–0.6)
0.3 (0.2–0.6)
0.70
1.7 (1.5–1.8)
1.7 (1.6–1.9)
1.4 (1.0–1.8)
0.10
1.9 (1.5–2.4)
1.4 (1.0–1.8)
0.06
8.3 (8.0–8.7)
8.6 (8.2–9.0)
6.7 (5.9–7.6)
<0.001
8.1 (7.2–9.1)
6.6 (5.8–7.4)
0.02
1-yr 10-yr Reintervention 30-day 1-yr 10-yr Myocardial infarction 30-day 1-yr 10-yr Deep sternal wound infection 30-day
0.5 (0.4–0.6)
0.5 (0.4–0.6)
0.5 (0.3–0.8)
0.60
0.4 (0.3–0.7)
0.6 (0.4–0.8)
0.50
1-yr
0.8 (0.7–0.9)
0.8 (0.7–0.9)
1.1 (0.8–1.5)
0.09
0.7 (0.5–1.1)
1.1 (0.8–1.5)
0.10
Values are % (95% confidence interval).
2248
Chikwe et al.
JACC VOL. 74, NO. 18, 2019
Multiarterial Versus Single-Arterial CABG
NOVEMBER 5, 2019:2238–48
repeat revascularization overall compared with multiarterial CABG. Venous compared with arterial bypass grafts were associated with reduced freedom from reintervention. These findings suggest that multiarterial surgical revascularization is underused
PERSPECTIVES COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Multiarterial surgical
in contemporary clinical practice and highlight the
revascularization is associated with superior survival,
need for targeted referral of younger patients likely to
graft patency, and freedom from myocardial infarc-
benefit from a multiarterial surgical revascularization
tion and repeat intervention.
strategy.
TRANSLATIONAL OUTLOOK: Future studies should compare outcomes associated with various
ADDRESS
FOR
CORRESPONDENCE:
Dr.
Joanna
types of second conduits when the left internal
Chikwe, Department of Cardiac Surgery, Smidt Heart
mammary artery is employed in multivessel surgical
Institute, Cedars-Sinai Medical Center, 8700 Beverly
revascularization.
Boulevard, Los Angeles, California 90048. E-mail: [email protected]. Twitter: @CedarsSinai.
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