Impact of Expeditious Management of Perioperative
Myocardial Ischemia in Patients Undergoing Isolated
Coronary Artery Bypass Surgery
Piroze M. Davierwala, MD; Alexander Verevkin, MD; Sergey Leontyev, MD;
Martin Misfeld, MD, PhD; Michael A. Borger, MD, PhD; Friedrich W. Mohr, MD, PhD
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Background—To analyze the effect of immediate treatment of perioperative myocardial ischemia (PMI) because of early
graft failure or incomplete revascularization in patients undergoing coronary artery bypass grafting (CABG) surgery.
Methods and Results—Between January 2004 and December 2010, 7461 patients underwent isolated CABG at our institution.
All patients showing evidence of PMI (n=399; 5.3% of total) underwent emergent coronary angiography. A total of 900
grafts and 1061 distal anastomoses were examined. Two hundred fifty-five patients had 360 distal anastomoses compromised
because of early graft failure or incomplete revascularization (ie, abnormal postoperative coronary angiogram). Revision
CABG or percutaneous coronary intervention was performed in 130 (51.0%) and 34 (13.3%) patients with abnormal
angiograms, respectively. Nonsurgical therapy was implemented in the remaining 91 patients (35.7%) with abnormal
angiograms. One hundred forty-four patients had normal postoperative graft-related angiograms. In-hospital mortality was
7.3% and 2.9% in patients with and without PMI (P<0.001). In patients with PMI, in-hospital mortality was 9.4% and
3.5% in patients with abnormal and normal postoperative angiograms, respectively (P=0.03). Significant multivariable
predictors of in-hospital mortality were hemodynamic deterioration, preangiography creatine kinase-MB isoenzyme rise
>2× normal, and time interval between primary CABG and coronary angiography >30 hours. Five-year survival in patients
without PMI (85.7±0.5%) was significantly better than those with PMI and abnormal angiograms (74.9±2.9%; P<0.001
log-rank). When in-hospital mortality was excluded, however, this difference in midterm survival disappeared (P=0.9).
Conclusions—PMI is associated with increased in-hospital mortality in patients undergoing isolated CABG.
Expeditious management of bypass graft failure results in similar midterm survival to nonischemic patients in hospital
survivors. (Circulation. 2013;128[suppl 1]:S226-S234.)
Key Words: bypass ◼ coronary ◼ ischemia ◼ morbidity ◼ mortality ◼ postoperative ◼ surgery
T
identify and correct the problem, and time lapse between primary CABG and corrective measures.
Coronary angiography (henceforth referred to as angiography) can accurately detect the cause of PMI, enabling immediate implementation of corrective measures (ie, percutaneous
coronary intervention [PCI] or revision CABG) and limiting
the extent of myocardial damage in patients with graft-related
problems. The time interval between primary CABG and angiography, as well as that between angiography and repeat intervention, may impact early and long-term post-CABG results.
The main objective of our study was to evaluate the effect of
various treatment options and time intervals on in-hospital and
midterm mortality in patients with PMI post-CABG.
he reported incidence of perioperative myocardial ischemia (PMI) after isolated coronary artery bypass grafting
(CABG) surgery ranges between 2% and 10%.1–3 It adversely
affects not only in-hospital morbidity and mortality4,5 but also
long-term survival.5,6 Although it can occur anytime during
the hospital stay, most published series have reported PMI
occurring within the first 72 hours after CABG.1,7 As diagnosis of PMI based solely on symptomatology in postoperative
patients is difficult, clinicians rely on electrocardiographic
alterations, significant elevations in cardiac enzyme levels,
new regional wall motion abnormalities on echocardiography,
repetitive ventricular arrhythmias, or hemodynamic instability as parameters to detect PMI. A delay in diagnosis results
in the development of myocardial infarction (MI),8 impairing postoperative ventricular function. PMI can be caused by
graft-related9 and nongraft-related problems.10,11 The extent of
cell damage depends on the number of grafts affected, area
of distribution of native vessels involved, measures taken to
Methods
Data Source
Clinical, operative, and outcome data were prospectively collected in
a computerized database for 7461 consecutive patients undergoing
From the Department of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany.
Presented at the 2012 American Heart Association meeting in Los Angeles, CA, November 3–7, 2012.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.
112.000347/-/DC1.
Correspondence to Piroze M. Davierwala, MD, Herzzentrum Leipzig, Struempellstraße 39, 04289 Leipzig, Germany. E-mail [email protected]
© 2013 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.112.000347
S226
Davierwala et al Myocardial Ischemia After Coronary Bypass Surgery S227
Table 1. Distribution of Preoperative Variables
Preoperative Variables
Group A n=130
Group B n=34
Group C n=91
Group D n=144
Total n=399
P Value
Age, y
67.7±9.7
67.0±10.5
69.8±9.1
66.9±9.1
67.8±9.4
0.1
Female
37 (28.5)
5 (14.7)
23 (25.3)
25 (17.4)
90 (22.6)
0.1
Diabetes mellitus
52 (40.0)
14 (41.2)
49 (53.8)
51 (35.4)
166 (41.6)
0.05
117 (90.0)
31 (91.2)
86 (94.5)
130 (90.3)
364 (91.2)
0.7
Systemic hypertension
Hyperlipidemia
91 (71.5)
23 (67.6)
75 (82.4)
111 (77.1)
302 (75.7)
0.2
COPD
7 (5.4)
6 (17.6)
5 (5.5)
7 (4.9)
25 (6.3)
0.04
CVA
5 (3.8)
3 (8.8)
9 (9.9)
9 (6.3)
26 (6.5)
0.3
25 (19.2)
19 (26.5)
18 (19.8)
39 (27.1)
91 (22.8)
0.5
Peripheral vascular
disease
Dialysis
2 (1.5)
0 (0.0)
1 (1.1)
2 (1.4)
5 (1.3)
0.9
LVEF, %
55±21
52±24
53±21
56±18
55±20
0.6
EF >60%
90 (69.2)
25 (73.5)
63 (69.2)
100 (69.4)
278 (69.7)
0.5
EF ≥30%–≤60%
32 (24.6)
5 (14.7)
23 (25.3)
36 (25.0)
96 (24.1)
0.5
5 (3.8)
4 (11.8)
5 (5.5)
7 (4.9)
21 (5.3)
0.5
Elective
97 (74.6)
21 (61.8)
69 (75.8)
102 (70.8)
289 (72.4)
0.9
Urgent
23 (17.7)
9 (26.5)
15 (16.5)
27 (18.8)
74 (18.5)
Emergent
10 (7.7)
4 (11.8)
7 (7.7)
14 (9.7)
35 (8.8)
5 (3.8)
2 (5.9)
1 (1.1)
5 (3.5)
13 (3.3)
0.5
EF <30%
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Priority of surgery
Critical preoperative
state
Cardiogenic shock
5 (3.8)
2 (5.9)
2 (2.2)
4 (2.8)
13 (3.3)
0.7
Preoperative MI
60 (46.2)
12 (35.3)
43 (47.3)
66 (45.8)
181 (45.4)
0.8
MI <48 h
17 (13.1)
1 (2.9)
10 (11.0)
17 (11.8)
45 (11.3)
0.4
Triple-vessel disease
95 (73.1)
25 (73.5)
69 (75.8)
102 (70.8)
291 (72.9)
0.9
Left main disease
48 (36.9)
11 (32.4)
25 (27.5)
53 (36.8)
137 (34.3)
0.4
Prior PCI
28 (21.5)
10 (29.4)
26 (28.6)
36 (25.0)
100 (25.1)
0.6
Prior cardiac surgery
Logistic EuroSCORE, %
4 (3.1)
2 (5.9)
4 (4.4)
8 (5.6)
18 (4.5)
0.8
5.7±7.3
10.0±17.9
7.6±11.4
7.1±10.2
7.0±10.6
0.2
Values expressed as mean±SD or n (%). Groups A, B, and C: patients with graft failure undergoing revision coronary bypass surgery, percutaneous coronary
intervention, and nonsurgical therapy, respectively. Group D: patients with normal coronary angiogram. COPD indicates chronic obstructive pulmonary disease;
CVA, cerebrovascular accident; EF, ejection fraction; LVEF, left ventricular ejection fraction; MI, myocardial infarction; and PCI, percutaneous intervention.
isolated CABG at the Leipzig Heart Center between January 2004
and December 2010. Of these, 4539 patients underwent on-pump
CABG, 2241 underwent off-pump CABG, and 681 underwent minimally invasive direct CABG. Patients undergoing combined cardiac
procedures were excluded from the analysis.
Of the total cohort, 399 consecutive patients (5.3%) who were diagnosed with PMI occurring within 7 days after primary surgery underwent
emergent postoperative angiography. An abnormal postoperative angiogram was defined as either early graft failure (stenotic or occluded grafts,
or faulty site of anastomosis) or incomplete revascularization. A normal
postoperative angiogram entailed a completely revascularized patient
(≥1 bypass graft performed to all significantly diseased native primary
arterial territories) with normal grafts (without significant stenoses, kinks,
twists, or occlusions). For the purpose of this study, we assigned the
patients to 4 groups depending on the treatment they received for PMI:
Groups A, B, and C: Patients with graft failure undergoing revision CABG, PCI, and nonsurgical therapy, respectively
Group D: Patients with no graft-related problems
The study was approved by our institutional ethics committee. Being
a retrospective study, individual patient informed consent was waived.
Preoperative Explanatory Variables
Table 1 shows the core baseline preoperative variables for the entire
patient cohort and for separate patient subgroups. Priority of surgery
was considered elective, urgent (operation during the same admission as cardiac catheterization or cardiac event), or emergent (operation within 24 hours of an event). Stenosis was considered significant
when ≥50% in the left main or ≥70% in other coronary arteries.
Intraoperative Parameters
Primary CABG was performed on-pump or off-pump (OPCAB) at
the discretion of the operating surgeon. The left anterior descending
artery was grafted by the left internal mammary artery in patients
who underwent minimally invasive direct CABG. Table 2 and Table
I in the online-only Data Supplement depict the intraoperative data.
Postoperative Management
All patients received intravenous acetylsalicylic acid 6 hours postoperatively and orally thereafter, if extubated. Addition of oral clopidogrel
for patients with diffuse coronary disease, endarterectomies, and offpump CABG was at the discretion of the operating surgeon. Patients
with recently implanted normally functioning coronary stents and
recent acute coronary syndromes also received dual antiplatelet therapy.
Twelve-lead ECGs were routinely performed immediately after surgery
and daily thereafter. Additional ECGs were performed as necessary.
Cardiac enzymes creatine kinase [CK]/CK-MB isoenzyme [CK/MD]
levels) were routinely assessed at 1, 6, 12, 24, and 48 hours after CABG
and thereafter only when elevated. Two-dimensional or transesophageal
S228 Circulation September 10, 2013
Table 2. Distribution of Intraoperative Variables
Intraoperative
Parameters
Group A n=130
Group B n=34
Group C n=91
Group D n=144
Total n=399
P Value
On-pump CABG
83 (63.8)
18 (52.9)
60 (65.9)
93 (64.6)
254 (63.7)
0.6
Off-pump CABG
41 (31.5)
9 (26.5)
23 (25.3)
33 (22.9)
106 (26.6)
0.4
Minimally invasive
direct CABG
6 (4.6)
7 (20.6)
8 (8.8)
18 (12.5)
39 (9.8)
0.02
Cardiopulmonary
bypass time, min
97±32
98±27
100±38
98±35
98±34
0.9
Aortic cross-clamp
time, min
56±28
60±17
56±34
55±35
56±30
0.9
210±61
204±58
207±58
203±60
206±60
0.8
Length of surgery, min
Values expressed as mean±SD or n (%). CABG indicates coronary artery bypass grafting.
echocardiography was performed to detect new regional wall motion
abnormalities and left ventricular function as required.
The decision to perform a postoperative emergent coronary angiogram in patients with a suspected diagnosis of PMI was made in
consultation with the operating surgeon, intensivist, and the treating
physician on the ward after detection of ≥1 of the following postoperative events: CK-MB levels >4× normal (normal values <24.6 U/L),
new ST-segment changes on ECG (ST elevation or depression, new
T-wave inversion, new left bundle-branch block), >1 episode of ventricular tachycardia or ventricular fibrillation, sudden cardiac arrest,
or unexpected or unexplained hemodynamic compromise (Figure 1).
Patients with angina-like symptoms who demonstrated other signs of
ischemia were also subjected to postoperative angiography.
CABG revision surgery was performed as soon as possible after angiography with an off-pump or on-pump without cardioplegic arrest
(ie, beating heart) method whenever possible. PCI was most often
performed at the time of postoperative angiography and mainly
addressed native coronary lesions. Anastomotic occlusions or stenoses were mostly revised by surgery. Nonsurgical therapy involved
inotropic and mechanical support (intra-aortic balloon pump or extracorporeal membrane oxygenation) for hemodynamically compromised patients and routine postoperative therapy in others.
60
Follow-up was performed by personal contact, mailed questionnaire,
or phone contact with patients and family members, with supplemental information supplied by family physicians and referring cardiologists. The closing interval was between August 2012 and November
2012. Overall, 42 patients were lost to follow-up, resulting in completeness of follow-up of 89.5%. Of these, 12, 7, 14, and 9 patients
were lost to follow-up at 1, 3, 5, and 8 years after surgery, respectively.
Outcomes
In-hospital mortality, defined as any postoperative death occurring
within the hospital stay of the primary operation, was our primary
outcome. Our secondary outcomes were midterm survival and freedom from major adverse cardiac and cerebrovascular events.
Data Analysis
Postangiography Treatment Strategy
All statistical analyses were performed using SPSS 17.0 (Chicago,
IL). Categorical variables were expressed as frequencies and percentages and compared using the χ2 or Fisher exact test. Continuous variables were expressed as mean±SD and compared by unpaired Student
t test or 1-way ANOVA. Of the 41 perioperative variables, those that
had a univariate P<0.05 or those judged to be clinically important
were submitted to a logistic regression model by stepwise selection.
Multivariate logistic regression methods were used to determine the
predictors of in-hospital mortality and are expressed as odds ratios
(OR) and 95% confidence intervals (CI). Model discrimination was
Group A
p=0.7
Group B
Group C
50
Group D
40
Percentage
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Postoperative Coronary Angiography
Follow-Up
p=0.3
30
p=0.9
20
p=0.1
p=0.3
p=0.1
10
0
ECG: New ST
changes
ECG: VT/VF
Angina
Cardiac arrest
Hemodynamic
deterioration
CK-MB > 4XN
Indications
Figure 1. Indications for postoperative coronary angiography according to patient groups. CK-MB >4×N indicates precoronary
angiography CK-MB levels >4× the normal values; and VT/VF, ventricular tachycardia/ventricular fibrillation.
Davierwala et al Myocardial Ischemia After Coronary Bypass Surgery S229
Table 3. Postoperative Coronary Angiography Findings in Patients With Early Graft Failure
Postoperative Angiographic
Findings
Group A n=130
Group B n=34
Group C n=91
Total n=255
No. of affected
anastomoses
<0.0001
0
2 (1.5)
12 (35.3)
1 (1.1)
1
56 (43.1)
15 (44.1)
75 (75)
2
54 (41.5)
4 (11.8)
11 (12.1)
69 (27.1)
3
17 (13.1)
3 (8.8)
4 (4.4)
24 (9.4)
4
1 (0.8)
0 (0.0)
0 (0.0)
1 (0.4)
Spasm
2 (1.5)
0 (0.0)
2 (2.2)
4 (1.6)
18 (52.9)
21 (23.1)
65 (25.5)
Incomplete
revascularization
P Value
26 (20)
15 (5.9)
146 (57.3)
0.7
<0.0001
Values expressed as n (%).
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assessed by the area under the receiver operating characteristic curve
and calibration by the Hosmer–Lemeshow goodness-of-fit statistic.
Event-free survival and freedom from major adverse cardiac and cerebrovascular event were calculated by Kaplan–Meier methods with
95% CI. Independent predictors of midterm survival were determined
with Cox proportional hazards analysis. Inclusion of covariates was
performed on the basis of clinical relevance or significance of univariate association. P<0.05 were considered statistically significant.
Results
Demographic Characteristics
Postoperative angiography identified early graft failure or
incomplete revascularization in 255 of the 399 patients diagnosed with PMI. Of these, 130 (51%) underwent revision
CABG (group A), 34 (13.3%) underwent PCI (group B),
and 91 (35.7%) were managed nonsurgically (group C). The
reasons for nonsurgical therapy were as follows: 5 patients
unsuitable for PCI were extremely ill or at very high risk to
undergo revision CABG, 11 patients had diffuse coronary
artery disease, 44 patients had significant competitive flow
in their native vessels, 4 patients were extremely stable with
no other signs of ischemia, and in 27 patients the cause was
unknown. No graft-related abnormalities were detected in 144
patients (group D).
The preoperative demographic profile of patients was
evenly distributed across all groups (Table 1). Ten percent of
patients, who underwent postoperative angiography for PMI,
had received minimally invasive direct CABG as the primary operation. These patients formed a fifth of the patients
who underwent PCI for PMI. Almost two-thirds of patients
received on-pump CABG and one-fourth off-pump CABG
Table 4. Time Intervals Between Various Events in
Groups A and B
Time Period Between, h (mean±SD) Group A
Group B
Group C
Primary CABG and coronary
angiogram
28±32
35±38
31±30
Coronary angiogram and repeat
revascularization
3.8±3.7 0.9±2.3
…
Peak CK-MB levels and repeat
revascularization
6.9±9.4 6.6±14.6
…
CABG indicates coronary artery bypass grafting.
P Value
0.2
<0.0001
0.9
as the primary operation (Table 2). The majority of patients
received 2 to 3 grafts with left internal mammary artery being
most frequently used. Most patients received 2 to 3 distal
anastomoses, with approximately one-quarter being sequential (Table I in the online-only Data Supplement).
Postoperative Coronary Angiogram
Figure 1 illustrates indications for postoperative angiography.
A total of 900 grafts and 1061 distal anastomoses were examined. Sixty-five patients had incomplete revascularization,
with the commonest reasons being a nondominant diseased
right coronary artery, a small or severely calcified target vessel, inability to find the target vessel, and attempts to avoid
hemodynamic compromise during high-risk off-pump CABG
surgery. These patients were mostly treated by PCI (Table 3).
Patients with >1 anastomotic problem frequently underwent
revision CABG. Two patients with graft spasm were treated
surgically as they had other failed grafts as well.
Repeat Intervention
Most revision CABGs in patients with abnormal postoperative angiograms were performed off-pump (63.8%), with
only a third performed on-pump and one with extracorporeal
membrane oxygenation support. Left anterior descending
artery grafts were most commonly revised (61.5%), followed by grafts to the first obtuse marginal (16.2%), posterior descending (14.6%), and circumflex, diagonal, and right
coronary arteries (7.7% each). Revision of the proximal
aortic and the Y-/T-anastomosis was required in 4.6% and
3%, respectively. A release of kinks or twists was performed
in 13.8% of patients. Conversely, only 14.7% of patients
treated by PCI underwent PCI to their left anterior descending artery. The circumflex (38.2%) and intermediate (26.4%)
arteries were the native vessels most commonly addressed
by PCI.
Postoperative Events and Outcomes
Table 4 represents the time interval between postoperative
events and procedures. In-hospital mortality for all patients
who underwent angiography for PMI (7.3%) was significantly
higher than that (2.9%) in patients undergoing CABG without evidence of PMI (P<0.001). Group D patients (3.5%)
S230 Circulation September 10, 2013
Table 5. Postoperative Outcomes
Postoperative
Outcomes
Group A
n=130
Group B
n=34
Group C
n=91
Group D
n=144
Low cardiac output
41 (31.5)
4 (11.8)
13 (14.3)
14 (9.7)
72 (18)
<0.0001
IABP insertion
48 (36.9)
5 (14.7)
15 (16.5)
18 (12.5)
86 (21.6)
<0.0001
ECMO implantation
Total
n=399
P Value
8 (6.2)
0 (0.0)
1 (1.1)
4 (2.8)
13 (3.3)
0.1
Peak CK-MB levels, U/L
156±186
132±192
126±144
96±108
126±156
0.02
MI
19 (14.6)
3 (8.8)
6 (6.6)
3 (2.1)
31 (7.8)
0.002
Resuscitation
19 (14.6)
5 (14.7)
12 (13.2)
18 (12.5)
54 (13.5)
0.9
Re-exploration for
bleeding
1 (0.8)
0 (0.0)
0 (0.0)
0 (0.0)
1 (0.3)
0.6
CVA
8 (6.2)
1 (2.9)
5 (5.5)
4 (2.8)
18 (4.5)
0.5
Sepsis
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8 (6.2)
0 (0.0)
3 (3.3)
6 (4.2)
17 (4.3)
0.4
New dialysis
26 (20.0)
1 (2.9)
11 (12.1)
15 (10.4)
53 (13.3)
0.03
Respiratory failure
31 (23.8)
8 (23.5)
19 (20.9)
21 (14.6)
79 (19.8)
Reintubation
69 (56.1)
6 (21.4)
15 (18.5)
22 (18.2)
112 (31.7)
<0.0001
Hospital stay, d
19±18
21±37
13±7
14±11
16±17
0.01
In-hospital death
14 (10.8)
2 (5.9)
8 (8.8)
5 (3.5)
29 (7.3)
0.1
0.2
Values expressed as mean±SD or n (%). CVA indicates cerebrovascular accident; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump;
and MI, myocardial infarction.
had a significantly lower mortality rate than groups A, B, and
C together (9.4%; P=0.03; Table 5). Of the 29 patients who
died in hospital, 21 were cardiac deaths, 3 patients each died
because of pneumonia and gastrointestinal complications, and
1 each because of sepsis and cerebrovascular accident.
Predictors of In-hospital Mortality
There was no association between the type of treatment
(revision CABG, PCI, or nonsurgical therapy) for abnormal postoperative angiograms and in-hospital mortality.
Univariate analysis revealed that the preoperative variables
MI within 48 hours of primary CABG (OR, 5.0; 95% CI,
2.2–11.6; P<0.0001), 3-vessel disease (OR, 3.9; 95% CI,
1.5–9.9; P=0.004), and emergency surgery (OR, 5.4; 95%
CI, 1.2–23.2; P=0.02) were strongly related to an increased
risk of in-hospital mortality. Postoperative events indicative
of PMI, including ventricular tachycardia/ventricular fibrillation (OR, 3.9; 95% CI, 1.8–8.6; P<0.0001), cardiac arrest
(OR, 2.9; 95% CI,1.3–6.7; P=0.01), hemodynamic deterioration (OR, 6.6; 95% CI, 2.3–18.8; P<0.0001), preangiography
CK-MB >2× normal (OR, 2.6; 95% CI, 1.1–6.1; P=0.04), and
time interval between primary CABG and angiography >30
hours (OR, 2.5; 95% CI, 1.2–5.3; P=0.02), were also associated with higher in-hospital mortality. However, multivariate
analysis revealed that only hemodynamic deterioration, preangiography CK-MB >2× normal, and time interval between
primary CABG and angiography >30 hours remained significant (Table 6).
Follow-Up
Midterm survival was similar in the 4 groups of patients
who underwent angiography for PMI (Figure 2). The 3- and
5-year survival for groups A, B, C, and D was 79.7±3.6%
and 75.1±4.0%, 90.6±5.2% and 77.3±8.4%, 78.5±4.4% and
75.5±4.7%, and 87.8±2.7% and 84.4±3.2% respectively
(P=0.1). Overall, 61 patients died during follow-up. Of these,
15 were cardiac deaths, 8 patients died because of sepsis, 5
because of pneumonia, 4 each from cerebrovascular accidents
and cancer, and 1 because of pulmonary embolism. The cause
of death in the 24 remaining patients was unknown. Factors
independently predictive of late mortality were age (OR, 1.1;
95% CI, 1.0–1.1; P<0.0001), diabetes mellitus (OR, 1.8; 95%
CI, 1.1–2.9; P=0.03), postoperative peak CK-MB levels (OR,
1.1; 95% CI, 1.0–1.2; P=0.01), time between primary CABG
and angiography (OR, 1.01; 95% CI, 1.00–1.01; P=0.008),
and hemodynamic deterioration (OR, 4.3; 95% CI, 1.7–10.4;
P=0.002). Freedom from major adverse cardiac and cerebrovascular event was lower in patients with PMI and abnormal
angiograms compared with those with normal graft-related
postoperative angiograms (Figure 3). The 3- and 5-year freedom from major adverse cardiac and cerebrovascular event
for groups A, B, C, and D was 69.7±4.1% and 60.2±4.6%,
88.1±7.0% and 60.9±10.4%, 76.2±4.5% and 73.2±4.8%,
82.4±3.1% and 76.9±3.8%, respectively (P=0.01).
Table 6. Multivariable Predictors of In-hospital Mortality in
Patients With PMI
Variable
Odds Ratio
95% CI
P Value
Emergency surgery
1.4
0.4–4.5
0.6
Postoperative cardiac arrest
1.7
0.6–5.1
0.3
Preoperative MI <48 h
2.4
0.8–7.1
0.1
Postoperative VT/VF
2.7
1.0–7.6
0.06
Time period between primary CABG and
coronary angiogram >30 h
2.9
1.2–7.2
0.02
Preangiography CK-MB >2× normal
3.7
1.3–10.5
0.01
Hemodynamic deterioration
6.1
1.8–20.8
0.003
Area under the receiver operating characteristic curve: 0.8; Hosmer–
Lemeshow goodness-of-fit: 0.9. CABG indicates coronary artery bypass grafting;
CI, confidence interval; MI, myocardial infarction; VF, ventricular fibrillation; and
VT, ventricular tachycardia.
Davierwala et al Myocardial Ischemia After Coronary Bypass Surgery S231
Figure 2. Groupwise patient survival.
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Midterm survival of the 255 patients with PMI and abnormal angiograms was significantly lower compared with that
of 7062 patients without evidence of PMI and 144 patients
with PMI, but with normal angiograms (Figure 4). The 5-year
survival for the above 3 categories of patients was 74.9±2.9%,
85.7±0.5%, and 87.8±2.8%, respectively (P=0.01) However,
no difference in survival was observed when in-hospital mortality was excluded (Figure 5).
Discussion
The present study is the largest and most comprehensive
analysis of the association between time intervals and treatment strategies and early and midterm outcomes in patients
undergoing postoperative emergent angiography for PMI
within 7 days of isolated CABG. Very few studies have
focused on this topic to date.1,7,9,12 The incidence of PMI was
5.3% in our patient population, which is higher than that in
previous studies. This can be partially explained by the fact
that patients presenting with signs of PMI ≤7 postoperative
days were included in our study compared with other series in
which patients were included ≤24 or 72 hours after surgery.1,7
Early postoperative graft failure and incomplete revascularization may cause myocardial hypoperfusion, resulting
in compromised ventricular function and low cardiac output
syndrome. Early graft failure commonly results from technical errors (eg, twisted or kinked grafts, improper proximal or
distal anastomoses, overstretched grafts, inappropriate site, or
vessel anastomosed), as well as graft spasm or thrombosis.2,9,13
If not addressed promptly, early graft failure can lead to irreversible myocardial damage, with subsequent effects on inhospital and long-term outcomes.14,15 Hence, close vigilance,
a high degree of suspicion, early postoperative angiography,
and expeditious treatment of PMI may be essential components of optimizing patient outcomes post-CABG.
Figure 3. Groupwise freedom from major adverse
cardiac and cerebrovascular events (MACCE).
S232 Circulation September 10, 2013
Figure 4. Survival including in-hospital mortality.
No perioperative myocardial ischemia (PMI): overall
population undergoing isolated coronary artery
bypass grafting without evidence of PMI; PMI with
abnormal coronary angiography (CA); PMI with
normal CA.
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Our study confirmed that a time interval between primary
CABG and postoperative angiography of >30 hours was not
only associated with higher in-hospital mortality but was also
independently predictive of late mortality. One can conclude
from this finding that prompt diagnosis and treatment of PMI
are required to avoid life-threatening complications of CABG
surgery. Despite our rather liberal approach to performing coronary angiography post-CABG, Table 4 shows that the mean
time interval between primary CABG and postoperative coronary angiogram exceeded 24 hours in all patient subgroups.
Shortening this time interval should have a beneficial effect
on early and late mortality because it would reverse myocardial ischemia before development of extensive myocardial
damage. One method of reducing this time interval would be
by reducing the threshold levels for performing a postoperative angiogram via strict adherence to a predefined protocol.
Although such an approach may increase the risk of cardiac
catheterization–associated complications, we are convinced
that the rate and severity of such complications are lower than
the risks associated with a delayed diagnosis and treatment
of PMI.
Definition and implementation of a post-CABG angiogram
protocol may best be performed by a heart-team approach
involving surgeons, cardiologists, and intensivists. In our institution, a consultant surgeon and an interventional cardiologist
are available on-site around the clock to facilitate quick and
effective decision making in patients with PMI. Despite this,
it is obvious there is still room for improvement with regard
to our time-to-angiography interval. Another possible method
for decreasing time to diagnosis and treatment would be the
development of a more sensitive marker for post-CABG PMI.
Although cardiac troponins are more sensitive than CK-MB in
Figure 5. Survival excluding in-hospital mortality.
No perioperative myocardial ischemia (PMI): overall
population undergoing isolated coronary artery
bypass grafting without evidence of PMI; PMI with
abnormal coronary angiography (CA); PMI with
normal CA.
Davierwala et al Myocardial Ischemia After Coronary Bypass Surgery S233
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the diagnosis of MI,16,17 its use in post-CABG patients is similarly limited by lack of specificity and various cutoffs used as
definitions for PMI.18
Another issue that contributed to our suboptimal CABGto-angiography interval is that the exact determination of the
onset of PMI is difficult in freshly operated CABG patients.
As a marker for onset of PMI, we, therefore, evaluated certain hard clinical end points in time (Table 4). The time interval between primary CABG and postoperative angiography
was shorter for revision CABG than PCI patients, probably
because of earlier development of signs of PMI in the former because these patients had a higher number of graft
failures per patient and more failed left anterior descending
artery grafts (Table 4). This time lag was similar to that previously mentioned in the literature (median time, 26 hours).9
Revascularization performed even ≤48 hours after initial onset
of ischemic symptoms is associated with a reduction in myocardial infarct size and better healing.19,20 There was no difference in delay to repeat revascularization from the time of
detection of peak CK-MB between the revision CABG and
PCI groups (Table 4). Although peak CK-MB indicates that
the infarct is already 12 to 14 hours old, it is the only hard
time point by which one can determine the approximate time
of onset of myocardial necrosis.
Another issue complicating the diagnosis of PMI is the fact
that 90% of CABG patients have some degree of CK-MB
elevation after revascularization.21 Hence, CK-MB levels
>5× normal have been used to define perioperative MI.22
Peak CK-MB levels can also be used to estimate the extent
of myocardial damage post-CABG. In the current study, the
peak CK-MB levels were significantly higher in patients
undergoing revision CABG because of the longer time interval between angiography and revision CABG, as well as the
greater number of graft problems and thus a larger myocardial
area at risk. On the contrary, patients with single graft problems or incomplete revascularization often received PCI. A
large proportion of patients who received nonsurgical therapy
had competitive flow in native vessels or failed grafts to very
small myocardial areas at risk and thus lower peak CK-MB
levels (Table 5).
Competitive flow in native vessels can result in early graft
failure. The use of functional imaging (ie, fractional flow
reserve) to guide revascularization may lower the risk of grafting vessels with competitive flow and subsequent graft failure.
Pijls et al23 concluded that fractional flow reserve seems useful in assessing the functional severity of moderately stenosed
coronary arteries and thereby the need for coronary revascularization. The investigators of the Fractional Flow Reserve
versus Angiography in Multivessel Evaluation study showed
that fractional flow reserve can delineate the functional significance of a coronary stenosis more accurately than angiography alone in patients with moderate (50%–70%) and severe
(70%–90%) stenoses.24
The in-hospital mortality in patients undergoing postoperative angiography for PMI after isolated CABG was 7.3%
in our study, which is <9.3% previously published from our
institution.12 Among the 3 treatment groups, patients undergoing revision CABG had the highest in-hospital mortality
(10.8%; Table 5). Postoperative low cardiac output syndrome,
use of intra-aortic balloon pump, postoperative MI, and newonset renal failure were also significantly higher in patients
undergoing revision CABG. Worse outcomes in this patients
group may be explained by the higher number of failed grafts
per patient, the higher peak CK-MB levels indicative of more
extensive myocardial damage, and the increased delay in
repeat revascularization. Similarly, Thielmann et al1 reported
a 30-day mortality of 12%, 20%, and 14.8% in patients subjected to revision CABG, PCI, and nonsurgical therapy for
PMI, despite a shorter time interval between primary CABG
and angiography than in our series. Laflamme et al7 also
reported an in-hospital mortality of 15.8% in patients treated
with CABG revision or PCI.
The factors that strongly predicted in-hospital mortality
in our study were postoperative CK-MB levels >2× normal,
hemodynamic deterioration, and a time delay of >30 hours
between primary CABG and coronary angiography. The
actual independent contribution of CK-MB levels >2× normal
is probably an overestimate because patients with massively
elevated CK-MB levels were also included in this group. One
can conclude from our study that episodes of unexpected or
unexplained hemodynamic deterioration should be immediately investigated with angiography so that repeat revascularization under cardiopulmonary resuscitation can be avoided.
A comprehensive analysis of midterm follow-up did not
reveal a significant difference in 5-year survival between the
4 groups of patients with PMI (Figure 2). However, when
survival of patients in groups A, B, and C were separately
compared with that of patients in group D, we found that only
patients managed nonsurgically (group C) had a significantly
lower survival (P=0.02) than those with normal postoperative
angiograms. One could conclude from this observation that
PMI should be treated more aggressively. Compared with
our overall population of patients undergoing isolated CABG
without evidence of PMI, the midterm survival of patients
with PMI was significantly worse (Figure 4). The major difference in survival is observed at the time of hospitalization,
after which the survival curves seem to even out and even
converge at the 6-year mark. One can, therefore, conclude
that the difference in midterm survival was mainly because
of the initial difference in in-hospital mortality. Indeed, the
difference in mortality disappeared after excluding in-hospital mortality (Figure 5). To validate this point, we individually compared the survival of patients with PMI with normal
and abnormal postoperative angiograms to patients without
PMI. The comparison made, with inclusion of in-hospital
mortality, revealed a significantly lower survival (P=0.01)
in patients with PMI with abnormal angiograms. This difference, however, disappeared (P=0.8) when in-hospital mortality was excluded. One can, therefore, conclude that earlier
postoperative angiography and treatment of bypass graft failure result in similar midterm survival to nonischemic patients
in hospital survivors.
Midterm mortality was strongly predicted by postoperative
hemodynamic deterioration, peak CK-MB levels, time period
between angiography and primary CABG, and preoperative factors such as age and diabetes mellitus. Postoperative
events, therefore, have a lasting effect even on mid- and probably long-term survival, thus confirming the importance of
S234 Circulation September 10, 2013
aggressive management of PMI. Many studies have reported
the negative impact of high postoperative CK-MB levels on
long-term outcomes.5,21
Study Limitations
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The current study is retrospective in nature and, therefore,
susceptible to all the inherent weaknesses thereof. The 4
groups compared have an inherent bias because the treatment
selected was based on the clinical situation of the patients at
the time of postoperative angiography. In addition, patients
with no graft failure are expected to have a lower risk of dying
compared with those with graft failure. However, the objective of this study was to determine whether the type of treatment had any impact on the early and midterm outcomes in
patients with graft failure and how they fared compared with
those without graft failure. Because the distribution of preoperative and intraoperative parameters and postoperative events
that were suggestive of PMI were fairly even among the 4
groups (Tables 1 and 2), we believe that the comparison of
these groups for this type of study is justified. Although the
completeness of follow-up in this study is suboptimal, the loss
of patients to follow-up seems to be random.
Conclusions
PMI is associated with an increased morbidity and mortality, even when judiciously and expeditiously managed.
Repeat revascularization for PMI can be performed significantly quicker with PCI than with CABG. In-hospital morbidity and mortality are significantly higher in patients who
undergo revision CABG for PMI, probably because of the
delay in achieving revascularization and a larger myocardial
area at risk because of multiple graft failures. Because the
time between primary CABG and angiography impacts early
and late outcomes, it is of prime importance to expedite the
coronary angiogram and the appropriate treatment as soon as
possible, especially in patients with unexplained postoperative
hemodynamic deterioration. Expeditious treatment of bypass
graft-related problems results in similar midterm survival to
nonischemic patients in hospital survivors.
Disclosures
None.
References
1.Thielmann M, Massoudy P, Jaeger BR, Neuhäuser M, Marggraf G,
Sack S, Erbel R, Jakob H. Emergency re-revascularization with percutaneous coronary intervention, reoperation, or conservative treatment in
patients with acute perioperative graft failure following coronary artery
bypass surgery. Eur J Cardiothorac Surg. 2006;30:117–125.
2.Jain U. Myocardial infarction during coronary artery bypass surgery.
J Cardiothorac Vasc Anesth. 1992;6:612–623.
3.Chaitman BR, Alderman EL, Sheffield LT, Tong T, Fisher L, Mock
MB, Weins RD, Kaiser GC, Roitman D, Berger R, Gersh B, Schaff H,
Bourassa MG, Killip T. Use of survival analysis to determine the clinical
significance of new Q waves after coronary bypass surgery. Circulation.
1983;67:302–309.
4. Force T, Hibberd P, Weeks G, Kemper AJ, Bloomfield P, Tow D, Josa M,
Khuri S, Parisi AF. Perioperative myocardial infarction after coronary
artery bypass surgery. Clinical significance and approach to risk stratification. Circulation. 1990;82:903–912.
5. Steuer J, Hoerte LG, Lindahl B, Stahle E. Impact of perioperative myocardial injury on early and long-term outcome after coronary artery bypass
surgery: Eur Heart J. 2002;23:1219–1227.
6.Namay DL, Hammermeister KE, Zia MS, DeRouen TA, Dodge HT,
Namay K. Effect of perioperative myocardial infarction on late survival
in patients undergoing coronary artery bypass surgery. Circulation.
1982;65:1066–1071.
7. Laflamme M, DeMey N, Bouchard D, Carrier M, Demers P, Pellerin
M, Couture P, Perrault LP. Management of early postoperative coronary artery bypass graft failure. Interact Cardiovasc Thorac Surg.
2012;14:452–456.
8. Slogoff S, Keats AS. Does perioperative myocardial ischemia lead to postoperative myocardial infarction? Anesthesiology. 1985;62:107–114.
9. Rasmussen C, Thiis JJ, Clemmensen P, Efsen F, Arendrup HC, Saunamäki
K, Madsen JK, Pettersson G. Significance and management of early graft
failure after coronary artery bypass grafting: feasibility and results of
acute angiography and re-re-vascularization. Eur J Cardiothorac Surg.
1997;12:847–852.
10.Franke U, Wahlers T, Cohnert TU, Koenig J, Rath NF, Wirsing M,
Haverich A. Retrograde versus antegrade crystalloid cardioplegia in
coronary surgery: value of troponin-I measurement. Ann Thorac Surg.
2001;71:249–253.
11.Thielmann M, Dörge H, Martin C, Belosjorow S, Schwanke U, van
De Sand A, Konietzka I, Büchert A, Krüger A, Schulz R, Heusch G.
Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha,
and sphingosine. Circ Res. 2002;90:807–813.
12. Fabricius AM, Gerber W, Hanke M, Garbade J, Autschbach R, Mohr FW.
Early angiographic control of perioperative ischemia after coronary artery
bypass grafting. Eur J Cardiothorac Surg. 2001;19:853–858.
13. Holmvang L, Jurlander B, Rasmussen C, Thiis JJ, Grande P, Clemmensen
P. Use of biochemical markers of infarction for diagnosing perioperative myocardial infarction and early graft occlusion after coronary artery
bypass surgery. Chest. 2002;121:103–111.
14. Breuer M, Schütz A, Gansera B, Eichinger W, Weingartner J, Kemkes B.
Intraoperative local fibrinolysis as emergency therapy after early coronary
artery bypass thrombosis. Eur J Cardiothorac Surg. 1999;15:266–270.
15.Mohl W, Simon P, Neumann F, Moidl R, Chevtchik O, Zweytick B,
Kupilik N, Wolner E. Analysis of left ventricular function after emergency
coronary artery bypass grafting for life-threatening ischaemia following
primary revascularization. Eur J Cardiothorac Surg. 1998;13:27–35.
16. Katus HA, Remppis A, Neumann FJ, Scheffold T, Diederich KW, Vinar
G, Noe A, Matern G, Kuebler W. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation. 1991;83:902–912.
17.Adams JE 3rd, Bodor GS, Dávila-Román VG, Delmez JA, Apple FS,
Ladenson JH, Jaffe AS. Cardiac troponin I. A marker with high specificity
for cardiac injury. Circulation. 1993;88:101–106.
18. Petäjä L, Salmenperä M, Pulkki K, Pettilä V. Biochemical injury markers
and mortality after coronary artery bypass grafting: a systematic review.
Ann Thorac Surg. 2009;87:1981–1992.
19.Schömig A, Mehilli J, Antoniucci D, Ndrepepa G, Markwardt C,
Di Pede F, Nekolla SG, Schlotterbeck K, Schühlen H, Pache J, Seyfarth M,
Martinoff S, Benzer W, Schmitt C, Dirschinger J, Schwaiger M, Kastrati
A; Beyond 12 hours Reperfusion AlternatiVe Evaluation (BRAVE-2) Trial
Investigators. Mechanical reperfusion in patients with acute myocardial
infarction presenting more than 12 hours from symptom onset: a randomized controlled trial. JAMA. 2005;293:2865–2872.
20. Pfisterer ME, Buser P, Osswald S, Weiss P, Bremerich J, Burkart F. Time
dependence of left ventricular recovery after delayed recanalization of an
occluded infarct-related coronary artery: findings of a pilot study. J Am
Coll Cardiol. 1998;32:97–102.
21.Brener SJ, Lytle BW, Schneider JP, Ellis SG, Topol EJ. Association
between CK-MB elevation after percutaneous or surgical revascularization and three-year mortality. J Am Coll Cardiol. 2002;40:1961–1967.
22. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen
EA, Kleiman NS, Mahaffey KW, Topol EJ, Pepine CJ, Lipicky RJ,
Granger CB, Harrington RA, Tardiff BE, Crenshaw BS, Bauman RP,
Zuckerman BD, Chaitman BR, Bittl JA, Ohman EM. Myonecrosis after
revascularization procedures. J Am Coll Cardiol. 1998;31:241–251.
23. Pijls NH, De Bruyne B, Peels K, Van Der Voort PH, Bonnier HJ, Bartunek
J Koolen JJ, Koolen JJ. Measurement of fractional flow reserve to assess
the functional severity of coronary-artery stenoses. N Engl J Med.
1996;334:1703–1708.
24. Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA, Ver Lee
PN, Maccarthy PA, Van’t Veer M, Pijls NH. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional
flow reserve versus angiography in multivessel evaluation. J Am Coll
Cardiol. 2010;55:2816–2821.
Impact of Expeditious Management of Perioperative Myocardial Ischemia in Patients
Undergoing Isolated Coronary Artery Bypass Surgery
Piroze M. Davierwala, Alexander Verevkin, Sergey Leontyev, Martin Misfeld, Michael A.
Borger and Friedrich W. Mohr
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Circulation. 2013;128:S226-S234
doi: 10.1161/CIRCULATIONAHA.112.000347
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2013 American Heart Association, Inc. All rights reserved.
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