670 THE NEV ENGLAND JOURNAL OF MEDICINE March 10, 1994

DIAGNOSIS OF PERIOPERATIVE MYOCARDIAL INFARCTION WITH MEASUREMENT OF

CARDIAC TROPONIN I
JESSE E. ADAMS III, M.D., GREGORIO A. SICARD, M.D., BRENT T. ALLEN, M.D., KEITH H. BRIDWELL, M.D.,
LAWRENCE G. LENKE, M.D., VICTOR G. DA.VILA-ROMAN, M.D., GEZA S. BODOR, M.D., PH.D.,
JACK H. LADENSON, PH.D., AND ALLAN S. JAFFE, M.D.
Abstract Background. Perioperative myocardial in- on the postoperative echocardiogram (that is, an abnor-
farction is the most common cause of morbidity and mor- mality that had not been seen on the preoperative echo-
tality in patients who have had noncardiac surgery, but its cardiogram) was considered to be indicative of periopera-
diagnosis can be difficult. The present study was designed tive infarction.
to determine whether the measurement of serum levels of Results. Eight patients who underwent vascular sur-
cardiac troponin 1, a highly sensitive and specific marker gery had new abnormalities in segmental-wall motion and
for cardiac injury, would help establish the diagnosis of received a diagnosis of perioperative infarction. All eight
myocardial infarction. had elevations of cardiac troponin 1, and six had elevations
Methods. We obtained preoperative measurements of of MB creatine kinase. Of the 100 patients without periop-
MB creatine kinase, total creatine kinase, and cardiac erative infarction detected by echocardiography, 19 had
troponin 1, in addition to base-line electrocardiograms and elevations of MB creatine kinase, and 1 had a slight eleva-
two-dimensional echocardiograms, in 96 patients under- tion of cardiac troponin 1.
going vascular surgery and 12 undergoing spinal surgery. Conclusions. The measurement of cardiac troponin I
Blood samples were obtained every 6 hours for at least is a sensitive and specific method for the diagnosis of
the first 36 hours after surgery, and electrocardiograms perioperative myocardial infarction. It avoids the high inci-
were obtained daily; a second echocardiogram was ob- dence of false diagnoses associated with the use of MB
tained approximately three days after surgery. The ap- creatine kinase as a diagnostic marker. (N EngI J Med
pearance of a new abnormality in segmental-wall motion 1 994;330:670-4.)

M YOCARDIAL infarction is the most common
cause of morbidity and mortality in patients
who have had noncardiac surgery.' The mortality
among patients with perioperative infarction ranges
from 36 to 70 percent.23 However, it can be difficult
to detect perioperative cardiac injury, since most epi-
sodes of myocardial ischemia occur without changes
in the heart rate or blood pressure.-',' Although
the measurement of MB creatine kinase has been
the marker of choice for the detection of myocardi-
al injury in most situations, increases above the nor-
mal range can sometimes occur after surgery in the
absence of apparent cardiac injury.67 Such false posi-
tive elevations have been attributed to injury of skel-
etal muscle occurring during surgery, since small
amounts of MB creatine kinase are present in healthy
skeletal muscle.79 Distinguishing elevations due to
myocardial injury from those due to skeletal-muscle
injury can be difficult. The measurement of MB cre-
atine kinase as a percentage of total creatine kinase
activity, which is sometimes used for this purpose, is
based on the premise that there is a higher percentage
of MB creatine kinase in cardiac muscle than in skel-
etal muscle.'0"' However, in practice, this ratio has
low sensitivity and variable specificity for cardiac in-
From the Cardiovascular Division (J.E.A., V.G.D.-R., A.S.J.), the Depart-
ment of Surgery, Vascular Surgery Section (G.A.S., B.T.A.), the Division of
Orthopedic Surgery (K.H.B., L.G.L.), and the Division of Laboratory Medicine
(J.H.L.), Washington University School of Medicine, St. Louis; and the Division
of Laboratory Medicine, Vanderbilt University, Nashville (G.S.B.). Address
reprint requests to Dr. Jaffe at Washington University School of Medicine, 660
S. Euclid, Box 8086, St. Louis, MO 63110.
Supported in part by grants (training grant 5-T32-ESO-7066 and Specialized
Center of Research grant in Coronary and Vascular Diseases HL 17646) from the
National Institutes of Health and by Baxter Diagnostics.
Dr. Ladenson is a consultant to Baxter Diagnostics, and Dr. Jaffe is a consult-
ant to Abbott Laboratories in the use of markers of myocardial injury. There are
licensing agreements between Washington University and Baxter Diagnostics in
the field of biochemical cardiovascular markers.
jury, especially when a concomitant injury of the skel-
etal muscle is present.12"3 Thus, it is often impossible
without further assessment to diagnose myocardial in-
jury in patients with elevated values of MB creatine
kinase or to exclude it from consideration. The de-
tection of abnormalities in segmental-wall motion
by transthoracic two-dimensional echocardiography
has been used to confirm the diagnosis of cardiac
injury in patients after surgery,'4 but echocardiog-
raphy may be less sensitive than MB creatine kinase
measurement for this purpose. In part because of
the difficulties of confirming the diagnosis, the re-
ported incidence of myocardial infarction in patients
undergoing noncardiac surgery varies widely (from
1 to 26 percent). 4"4"5 A serum marker that had a
higher specificity for cardiac injury than MB creatine
kinase and as high a sensitivity would facilitate the
detection and treatment of perioperative myocardial
infarction.
Cardiac troponin I is a regulatory protein with a
high specificity for cardiac injury.'2"16"7 It is not found
in skeletal muscle during neonatal development or
during adulthood, even after acute or chronic injury of
the skeletal muscle.'6-"' Accordingly, elevations do not
occur in plasma, even in patients with acute or chronic
skeletal muscle disease, unless acute myocardial in-
jury is present.'2 Recent data indicate that the sen-
sitivity of cardiac troponin I is similar to that of
MB creatine kinase for the diagnosis of acute myo-
cardial infarction.'9'20 Furthermore, elevations of car-
diac troponin I persist for up to five to seven days in
plasma, 19'21 permitting flexibility in the timing of
blood sampling. Our study was designed to determine
whether the measurement of cardiac troponin I would
allow for the distinction between patients with periop-
erative elevations of MB creatine kinase due to skel-
etal-muscle injury and those with elevations due to

The New England Journal of Medicine

Downloaded from nejm.org on January 8, 2019. For personal use only. No other uses without permission.
Copyright © 1994 Massachusetts Medical Society. All rights reserved.
Vol. 330 No. 10 DIAGNOSIS OF PERIOPERATIVE MYOCARDIAL INFARCTION
myocardial injury, and also to determine the incidence
of false positive elevations of MB creatine kinase after
surgery.
METHODS
One hundred twenty-nine consecutive patients undergoing vas-
cular or spinal surgery were enrolled in the study. Patients requiring
vascular surgery were chosen because this group has a high inci-
dence of coronary artery disease, which increases the risk of periop-
erative myocardial infarction. A smaller cohort of patients requiring
surgery for spinal deformities (n = 12) was also studied, since such
patients frequently have perioperative elevations of MB creatine
kinase.7 To be eligible for this study, patients had to be admitted to
the hospital at least one day before surgery to allow for preoperative
echocardiography. Thirteen patients were excluded because the
echocardiographic views were inadequate for the evaluation of ab-
normalities in segmental-wall motion in any region of the left ventri-
cle (that is, at least 80 percent of the endocardium of each segment
could not be visualized on either the preoperative or postoperative
echocardiogram), three were excluded because their electrocardio-
grams showed a left bundle-branch block or a paced rhythm, two
were excluded because they had had a myocardial infarction in the
previous seven days, two refused to give informed consent, and one
died before blood samples could be obtained. Of the remaining 108
patients, 96 underwent vascular surgery, and 12 underwent spinal
surgery. Preoperative studies in all patients included measurements
of total creatine kinase activity, MB creatine kinase mass (that is,
the quantity of protein per milliliter of serum), and cardiac tropo-
nin I mass, as well as electrocardiography and base-line echocardi-
ography. The measurements were repeated every 6 hours for the
first 36 hours after surgery, and electrocardiograms were obtained
daily. A second echocardiogram was obtained three to five days
after surgery. The protocol was approved by the Human Studies
Committee of Washington University School of Medicine.
All echocardiograms were obtained with an ultrasound imaging
system (HP 77600; Hewlett-Packard, Andover, Mass.) with either
a 2.5- or 3.5-MHz transducer. Two-dimensional echocardiographic
images were obtained in the parasternal short- and long-axis views,
apical two- and four-chamber views, and subcostal views, as recom-
mended by the American Society of Echocardiography.22 All echo-
cardiograms were interpreted by an expert echocardiographic read-
er who was unaware of the clinical and biochemical information.
The reader was not told which echocardiogram was obtained preop-
eratively, and which postoperatively. A 16-segment model, as rec-
ommended by the American Society of Echocardiography, was
used to detect and quantify any abnormalities of regional-wall mo-
tion,23 which were classified as 1 (normal), 2 (hypokinetic), 3 (aki-
netic), or 4 (dyskinetic). The development of postoperative akinesis
or dyskinesis in any segment that had been normal or hypokinetic
on the preoperative echocardiogram was considered indicative of an
infarction. Thirty-three echocardiograms, including all those with
differences between the preoperative and postoperative studies,
were reread to determine the intraobserver variability. The con-
cordance between the initial and subsequent readings for the diag-
nosis of myocardial infarction was 100 percent. The same echocar-
diograms were read by a second expert echocardiographer to
determine the interobserver variability. The presence or absence of
a difference between preoperative and postoperative studies was
concordant in 32 of the 33 echocardiograms. In one, the second
reader thought that the views obtained were inadequate for a diag-
nosis.
Evaluation of Molecular Markers
Blood samples were drawn into tubes with no preservatives and
centrifuged at 2000Xg for 15 minutes. Serum was stored at -70°C,
thawed once, and assayed in batches. Total creatine kinase, MB
creatine kinase, and cardiac troponin I are stable when handled in
this manner.21 2425 Assays and determinations of abnormal values
were performed by technicians who were unaware of the clinical
and echocardiographic data.
Total creatine kinase activity (upper reference limit, 220 IU per
liter; limit of detection, 25) was measured on a Flexigem centrifugal
analyzer (Electro-Nucleonics, Columbia, Md.) 25
The New England Journal of Medicine
Downloaded from nejm.org on January 8, 2019. For personal use only. No other uses without permission.
Copyright © 1994 Massachusetts Medical Society. All rights reserved.
- ADAMS ET AL. 671
MB creatine kinase mass (upper reference limit, 6.7 ng per milli-
liter; limit of detection, 2.2) was measured with a commercial-
ly available immunioassay (Stratus CK-MB; Baxter Diagnostics,
Miami) .24
Cardiac troponin I mass was measured with an immunoassay in a
preliminary application on the Baxter Stratus analyzer, which uses
two monoclonal antibodies specific for cardiac troponin I that rec-
ognize different epitopes.2 Cardiac troponin I is undetectable in
normal volunteers. A parametric analysis of this assay in hospital-
ized patients without myocardial infarction has established that the
upper limit of the reference range is 3.1 ng per milliliter, given a 95
percent cutoff value; the limit of detection is 1.5 ng per milliliter.
The immunoassay has no detectable cross-reactivity with human
skeletal-muscle troponin 1.21
Statistical Analysis
The significance (two-tailed test) and confidence intervals for
differences in the incidence of elevations of cardiac troponin I and
MB creatine kinase were calculated by McNemar's test.26
RESULTS
Table 1 shows the demographic and clinical charac-
teristics of the 108 patients enrolled in the study. Eight
patients had new abnormalities of segmental-wall mo-
tion on the postoperative echocardiogram and re-
ceived a diagnosis of perioperative myocardial infarc-
tion. All eight patients had elevated cardiac troponin I
values (Fig. 1), and six of the eight had elevated MB
creatine kinase values (Fig. 2). The cardiac troponin I
values in the eight patients with infarction are shown
in Figure 3. Nineteen of the patients without echocar-
diographic evidence of a myocardial infarction (8 of
whom had undergone spinal surgery, and 11 vascular
surgery) had elevated values of MB creatine kinase;
only 1 patient had an elevated level of cardiac tropo-
nin I. The difference between the specificity of cardiac
troponin I (99 percent) and that of MB creatine ki-
nase (81 percent) was significant (P<0.005). The
standard error for this 18 percent difference was 4.1
percent, and the confidence interval was 10 to 26 per-
cent. The lone patient who had an elevation of cardiac
troponin I but no new abnormality of regional-wall
motion had prolonged severe hypotension (systolic
pressure, 60 mm Hg) and sinus tachycardia (heart
rate, 150 beats per minute) immediately after surgery,
with new deep depression of the ST segments in the
inferolateral leads. Subsequently, she had a minor ele-
vation of cardiac troponin I to 3.3 ng per milliliter
(upper reference limit, 3. 1) and an increase (and then
Table 1. Characteristics of 108 Patients Undergoing
Noncardiac Surgery.
VASCULAR SPINAL
SURGERY SUaaY
C}ARACTERIC (N = 96) (N - 12)
Age (Y)* 67.4±10.7 42.6±23.2
Sex (M/F) 50/46 7/5
odition ieq'umWg surgery
.(no. of padents)
`Ao-eiwc damage - 57
With abdominal aortic seurysm 33
,P~hLJVascular. diseas 39
mardik ti y 4
*Phis..- vWbu m_n *SD.
672 TIHE NEN ENGLANI) JOURNAL OF IMEDICINE
a decrease) in MB creatine kinase to a peak level of 6.5
ng per milliliter (upper reference limit, 6.7). However,
no new abnormalities of segmental-wall motion were
identified. Two of the eight patients with periopera-
tive myocardial infarction had Q waves on subsequent
electrocardiograms; the other six had only ST-seg-
ment or T-wave changes (that is, none had Q-wave
infarctions); two had symptoms (hypotension, short-
ness of breath, or both). Thirty-two of the 100 pa-
tients without evidence of an infarction on echocardi-
ography and without elevations of cardiac troponin I
also had nonspecific changes in the ST segment or
T wave after surgery.
The patients with perioperative myocardial infarc-
tion generally had higher ratios of MB creatine kinase
to total creatine kinase (Fig. 4). XVith the use of peak
values and a cutoff ratio of 2.5," which is equivalent
to a cutoff value of 5 percent if activity rather than
mass is measured,' calculation of this ratio yielded a
sensitivity of 62.5 percent.
Three patients undergoing vascular surgery died
during hospitalization. Each had a perioperative myo-
cardial infarction diagnosed on the basis of changes in
cardiac troponin I and confirmed by serial echocar-
diograms. No other patients died. None of the patients
undergoing surgery for spinal deformities had a pern-
operative myocardial infarction. The patients who
had infarctions were hospitalized longer than those
who did not (mean [±SD], 29+24.6 days vs. 9.8+ 7.4
days, respectively).
DISCUSSION
These data indicate that serial measurements of
cardiac troponin I provide a highly accurate method
of detecting perioperative myocardial infarction or ex-
cluding the diagnosis. There was a concordance be-
tween the development of abnormalities in segmental-
wall motion, as detected by echocardiography, and
elevations in cardiac troponin I in 107 of the 108 pa-
tients in the study. In one patient, a minor elevation of
cardiac troponin I occurred after prolonged hypoten-
sion, tachycardia, and electrocardiographic changes,
but new wall-motion abnormalities were not detected
by echocardiography. This patient may have had a
c .. t ; .^ :. . ; ......... ' 't ing
* (69.9)
.
(65.4)
:... q:,y.. 0~*(42.1)
~ ~ ~(32.5) Our study protocol provided for an extensive periop-
2U -0;v;e-#(57
0E
Pafio s 8..9; ; Patients
without Infaron with Infarction
Figure 1. Peak Cardiac Troponin Mass in Patients with and
without Perioperative Myocardial Infarction.
The upper reference limit for cardiac troponin mass is 3.1 ng per
milliliter. The triangles denote patients undergoing spinal surgery,
and the circles those undergoing vascular surgery.
The New England Journal of Medicine
Downloaded from nejm.org on January 8, 2019. For personal use only. No other uses without permission.
Copyright © 1994 Massachusetts Medical Society. All rights reserved.
Mlarch 10, 1994
- * (S1.8). * (87t.8)
40
C 35.
CD
30
*25
20 ij
0 15
00
'-
*-'.
^~~~~ ~ ~~~~~~~~~ *xf-
0
*witho fr4;j@ct nwEi
Xm.
Figure 2. Peak MB Creatine Kinase Mass in Patients with and
without Perioperative Myocardial Infarction.
The upper reference limit for MB creatine kinase mass is 6.7 ng
per milliliter. The triangles denote patients undergoing spinal sur-
gery, and the circles those undergoing vascular surgery.
small amount of myocardial damage. It is likely that
cardiac troponin I, a sensitive marker of myocardial
injury, detects smaller amounts of myocardial damage
than even high-quality serial echocardiograms. In
contrast, MB creatine kinase was elevated in 19 per-
cent of the patients without perioperative cardiac in-
jury, including two thirds of those undergoing spinal
surgery, which is consistent with the results of previ-
ous studies.6'7 Among the patients undergoing vascu-
lar surgery, false positive elevations of MB creatine
kinase were more common than true positive eleva-
tions (occurring in 11 and 6 patients, respectively). It
is unlikely that the high incidence of false positive
increases in MB creatine kinase was due to more sensi-
tive detection of infarction. Although MB creatine
kinase may be more sensitive than even serial echocar-
diograms in some cases, we and others have docu-
mented that measurements of cardiac troponin I and
MB creatine kinase have a similar sensitivity for the
diagnosis of acute infarction. 2' In addition, our data
are consistent with an extensive literature document-
' ' 'elevations
' ' ' J * (113)
of MB creatine kinase in association
with acute and chronic skeletal-muscle injury.67'32728
erative cardiovascular evaluation in an attempt to
exclude the possibility of even small amounts of myo-
cardial injury. Our data strongly support the view that
in many cases perioperative elevations of MB cre-
atine kinase result from damage to skeletal muscle
rather than a cardiac injury. Thus, the measurement
of a highlly sensitive, cardiac-specific marker such as
cardiac troponin I should improve the perioperative
evaluation and care of patients who undergo non-
cardiac surgerv. Our data do not establish the supe-
rior sensitivity of cardiac troponin I as compared
with MB creatine kinase, only its superior specificity
for the detection of perioperative infarction.
Vol. 330 No. 10 DIAGNOSIS OF PERIOPERATlIVE MYOCARDIAL INFARClITON - AD)AMS El ALI. 67'S

consistent with previous reports of a mortality rate of

36 to 70 percent associated with perioperative myocar-
:20 2120 dial injury.2 3'29 The patients with perioperative cardi-
ac injury also required a longer hospitalization than
p -~~~~~~~~~~~~~~~~~-- those without infarction. In some cases the mvocardial
08 121 I 24 0 68 &'12
infarction may have been responsible, but in others
Hours after Surgery Hours after Surgery the cardiac injury appeared to be due to noncardiovas-
cular complications. Although knowledge of the pres-
;Sq. i .F.sF
4.0 . - ...........
30 - ence of myocardial damage might have facilitated the
care of these patients, aggressive hemodyniamic moni-
o 0 toring was routinely employed. Further studies will be
necessary to determine whether the detection of cardi-
ac injury in such patients can improve their prognosis.
'-'1mSs$t4p
3''s'1a -,,12 0.8.61218
0 24 30342 The greater specificity of cardiac troponin I, as
i?, . ; 91§ i t ¢.!:jv Hors after Surgery compared with MB creatine kinase, for the detec-
' / 8--@ 2,~jq:.2
tion of myocardial injury is consistent with their
molecular properties. The B subunit of creatine ki-
;itpw 30 nase, though prevalent in fetal skeletal muscle, is
produced to only a small extent in healthy adult skel-
9= ).j60 <1 18 20 12S4~s
etal muscle.' Like many proteins, including cardiac
troponin T, that are expressed during fetal develop-
F14#t9ss4gory _
~$ey~ ment, B-chain creatine kinase increases substantially
Hogwafter Surgery in adult skeletal muscle after injury.31 In contrast,
eso C 70
there are molecular forms of troponin I with unique
amino acid sequences in slow- and fast-twitch skeletal
20 muscle and cardiac muscle.31 lThus, unlike both MB
10~~~~S 0
creatine kinase and other troponin proteins, cardiac
2Cl 10
rw
rioks _. _1
troponin I is produced only in myocardium through-
4Af^.t1
i.44248 0 '-.130 36 out development. 16,111,32 At present, cardiac troponin I
A?Bwefterurpy Hour. after Surgery is the only known molecular marker of myocardial
Figure 3. Time Course of Changes in Cardiac Troponin Levels injury that is not expressed in regenerating skeletal
after Surgery in Eight Patients with Acute Infarction. muscle.'167'33'34 For this reason, it is not elevated
Initial elevations were present in six patients on day 1 and in two in plasma from patients with acute or chronic mus-
patients on day 2. The broken lines denote the upper limit of cle disease unless a cardiac injury has occurred.'2"'7
normal values. Preoperative values are indicated by the first sym- Although not directly proved in our study, it is likely
bol in each curve.

Although a few patients had obvious infarctions,

most had a smaller degree of myocardial injury, which
can be more difficult to diagnose. Thirty-two patients E ;2 se
- - **+4XJi(W5 >
had nonspecific electrocardiographic changes of un- co
j
0
certain importance, and 25 of the 32 had increased
MB creatine kinase values, but only 6 of these 32
patients (19 percent) were found to have echocardio-
graphic evidence of myocardial injury. Thus, al-
though electrocardiographic monitoring frequently 2.0
detects episodes of perioperative myocardial ischemia
that are not otherwise apparent,5 this approach is not
specific for perioperative myocardial infarction. Our c . 9 . . ,

data suggest that the use of the ratio of MB creatine Kinase,, Acivity in Painswt:n ihu
kinase mass to total creatine kinase activity improves eiprtv ycr
the accuracy of creatine kinase as a diagnostic marker
but does not provide the sensitivity afforded by the
measurement of cardiac troponin I. Furthermore, in
many situations, the use of this ratio is inaccurate in
differentiating skeletal-muscle injury from myocardial
injury. 12,13,27
The patients with perioperative myocardial infarc- ~~7~WittioU dinal tinfawction
tions had increased morbidity and mortality during
hospitalization, as compared with the patients who The suggested reference limit for the ratio is 2.5. The triangles
did not have infarctions. Three of the eight patients denote patients undergoing spinal surgery, and the circles those
with infarctions died before discharge. This finding is undergoing vascular surgery.

The New England Journal of Medicine

Downloaded from nejm.org on January 8, 2019. For personal use only. No other uses without permission.
Copyright © 1994 Massachusetts Medical Society. All rights reserved.
674 THE NEW ENGLAND JOURNAL OF MEDICINE
that the specificity of cardiac troponin I is not affected
by the type of surgery that patients undergo.
Since elevations of cardiac troponin I persist for five
to seven days after myocardial injury, the use of this
marker to diagnose perioperative myocardial infarc-
tion will probably require one of two diagnostic strate-
gies. One strategy is to measure cardiac troponin I
only if a myocardial injury is suspected and the values
of MB creatine kinase are elevated. An alternative
strategy is to obtain a preoperative value for compari-
son with postoperative values. A refined method of
detecting perioperative infarction should improve the
ability to predict which patients are at risk of an in-
farction and to determine its effect on the short- and
long-term prognosis.
The variable results reported in the extensive litera-
ture on this topic probably reflect the difficulties of
diagnosing myocardial injury perioperatively. For ex-
ample, among the patients in our study who under-
went vascular surgery, the incidence of perioperative
myocardial infarction (8.3 percent) and death (3.1
percent) was higher than in previous studies, includ-
ing one from our institution.' 429,35-37 The likely expla-
nation is that we diagnosed infarctions that might
have been missed in other studies. In addition, since
the patients in our study had to be admitted at least
one day before surgery in order to obtain a preoper-
ative echocardiogram, patients at low risk admitted
just before surgery could not be enrolled. Finally, all
the patients in our study who had vascular surgery
underwent extensive procedures (Table 1). Thus, en-
rollment in our study was biased in favor of patients
with an increased risk of cardiovascular injury.
The measurement of cardiac troponin I is an accu-
rate method to confirm or exclude the diagnosis of
perioperative cardiac injury. Its use should be simpler
and more cost effective than the routine use of echo-
cardiography. Moreover, the improved detection of
perioperative myocardial infarction should help clari-
fy the true incidence, predictive factors, and prognos-
tic importance of perioperative cardiac injury.
We are indebted to Dr. William Hopkins for the echocardio-
graphic review, to Dr. Philip Miller for statistical consultation, to
V. Landt for technical assistance, to S. Gilvary, R.D.C.S., for echo-
cardiographic assistance, and to S. Viviano for assistance in the
preparation of the manuscript.
REFERENCES
1. Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990;72:
153-84.
2. Roberts SL, Tinker JH. Cardiovascular disease, risk, and outcome in anes-
thesia. Philadelphia: J.B. Lippincott, 1988:33-49.
3. London MJ, Mangano DT. Assessment of perioperative risk. In: Stoelting
RK, ed. Advances in anesthesia. Vol. 5. Chicago: Year Book Medical,
1988:53-87.
4. Mangano DT, Browner WS, Hollenberg M, et al. Association of periopera-
tive myocardial ischemia with cardiac morbidity and mortality in men un-
dergoing noncardiac surgery. N Engl J Med 1990;323:1781-8.
5. Mangano DT, Hollenberg M, Fegert G, et al. Perioperative myocardial
ischemia in patients undergoing noncardiac surgery - I: incidence and
severity during the 4 day perioperative period: the Study of Perioperative
Ischemia (SPI) Research Group. J Am Coll Cardiol 199 1;17:843-50.
6. Wukich DK, Callaghan JJ, Graeber GM, Martyak T, Lyon JJ. Operative
treatment of acute hip fractures: its effect on serum creatine kinase, lactate
dehydrogenase and their isoenzymes. I Trauma 1989;29:375-9.
7. Lenke LG, Bridwell KH, Jaffe AS. Increases in creatine kinase MB isoen-
zyme levels following spinal surgery. J Spinal Disord (in press).
The New England Journal of Medicine
Downloaded from nejm.org on January 8, 2019. For personal use only. No other uses without permission.
Copyright © 1994 Massachusetts Medical Society. All rights reserved.
March 10, 1994
8. Tsung JS, Tsung SS. Creatine kinase isoenzymes in extracts of various
human skeletal muscles. Clin Chem 1986;32:1568-70.
9. Trask RV, Biladello JJ. Tissue-specific distribution and developmental reg-
ulation of M and B creatine kinase mRNAs. Biochim Biophys Acta
1990;1049: 182-8.
10. el Allaf M, Chapelle JP, el Allaf D, et al. Differentiating muscle damage
from myocardial injury by means of the serum creatine kinase (CK) isoen-
zyme MB mass measurement/total CK activity ratio. Clin Chem 1986;32:
291-5.
11. Wolfson D, Lindberg E, Su L, Farber SJ, Dubin SB. Three rapid immuno-
assays for the determination of creatine kinase MB: an analytical, clinical
and interpretive evaluation. Am Heart J 1991;122:958-64.
12. Adams JE III, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I: a
marker with high specificity for cardiac injury. Circulation 1993;88:101-6.
13. Potkin RT, Weiner JA, Trobaugh GB, et al. Evaluation of noninvasive tests
of cardiac damage in suspected cardiac contusion. Circulation 1982;66:627-
31.
14. Force T, Kemper AJ, Bloomfield P, et al. Non-Q wave perioperative myo-
cardial infarction: assessment of the incidence and severity of regional dys-
function with quantitative two-dimensional echocardiography. Circulation
1985;72:78 1-9.
15. Sullivan CA, Rohrer MJ, Cutler BS. Clinical management of the sympto-
matic but unruptured abdominal aortic aneurysm. J Vasc Surg 1990; 11:799-
803.
16. Toyota N, Shimada Y. Differentiation of troponin in cardiac and skeletal
muscles in chicken embryos as studied by immunofluorescence microscopy.
J Cell Biol 1981;91:497-504.
17. Cummins P, Young A, Auckland ML, Michie CA, Stone PCW, Shepstone
BJ. Comparison of serum cardiac specific troponin-I with creatine kinase,
creatine kinase-MB isoenzyme, tropomyosin, myoglobin and C-reactive
protein release in marathon runners: cardiac or skeletal muscle trauma? Eur J
Clin Invest 1987;17:317-24.
18. Martin AF, Orlowski J. Molecular cloning and developmental expression of
the rat cardiac-specific isoform of troponin I. J Mol Cell Cardiol 1991;23:
583-8.
19. Cummins B, Auckland ML, Cummins P. Cardiac-specific troponin-I radio-
immunoassay in the diagnosis of acute myocardial infarction. Am Heart
J 1987; 1 13:1333-44.
20. Larue C, Calzolari C, Bertinchant JP, Leclercq F, Grolleau R, Pau B.
Cardiac-specific immunoenzymometric assay of troponin I in the early
phase of acute myocardial infarction. Clin Chem 1993;39:972-9.
21. Bodor GS, Porter S, Landt Y, Ladenson JH. Development of monoclonal
antibodies for an assay of cardiac troponin-I and preliminary results in
suspected cases of myocardial infarction. Clin Chem 1992;38:2203-14.
22. Henry WL, DeMaria A, Gramiak R, et al. Report of the American Society
of Echocardiography Committee on Nomenclature and Standards in Two-
Dimensional Echocardiography. Circulation 1980;62:212-5.
23. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantita-
tion of the left ventricle by two-dimensional echocardiography. J Am Soc
Echocardiogr 1989;2:358-67.
24. Vaidya HC, Maynard Y, Dietzler DN, Ladenson JH. Direct measurement of
creatine kinase-MB activity in serum after extraction with a monoclonal
antibody specific to the MB isoenzyme. Clin Chem 1986;32:657-63.
25. Rosalki SB. An improved procedure for serum creatine phosphokinase de-
termination. J Lab Clin Med 1967;69:696-705.
26. Snedecor GW, Cochran WG. Statistical methods. 7th ed. Ames: Iowa State
University Press, 1980:121-3.
27. Keshgegian AA, Feinberg NV. Serum creatine kinase MB isoenzyme in
chronic muscle disease. Clin Chem 1984;30:575-8.
28. Tsung SH. Several conditions causing elevation of serum CK-MB and CK-
BB. Am J Clin Pathol 1981;75:711-5.
29. Jamieson WRE, Janusz MT, Miyagishima RT, Gerein AN. Influence of
ischemic heart disease on early and late mortality after surgery for peripheral
occlusive vascular disease. Circulation 1982;66:Suppl 1:1-92-I-97.
30. Apple FS, Rogers MA, Sherman WM, Costill DL, Hagerman FC, Ivy JL.
Profile of creatine kinase isoenzymes in skeletal muscles of marathon run-
ners. Clin Chem 1984;30:413-6.
31. Wilkinson JM, Grand RJA. Comparison of amino acid sequence of troponin
I from different striated muscles. Nature 1978;271:31-5.
32. Ausoni S, De Nardi C, Moretti P, Gorza L, Schiaffino S. Developmental
expression of rat cardiac troponin I mRNA. Development 1991;1 12:1041-51.
33. Saggin L, Gorza L, Ausoni S, Schiaffino S. Cardiac troponin T in develop-
ing, regenerating, and denervated rat skeletal muscle. Development 1990;
110:547-54.
34. Adams JE III, Abendschein DR, Jaffe AS. Biochemical markers of myocar-
dial injury: is MB creatine kinase the choice for the 1990's? Circulation
1993;88:750-63.
35. Hertzer NR, Avellone JC, Farrell CJ, et al. The risk of vascular surgery in a
metropolitan community: with observations on surgeon experience and hos-
pital size. J Vasc Surg 1984;1:13-21.
36. Hollier LH, Taylor LM, Ochsner J. Recommended indications for operative
treatment of abdominal aortic aneurysms. J Vasc Surg 1992;15:1046-56.
37. Sicard GA, Allen BT, Munn IS. Anderson CB. Retroperitoneal versus
transperitoneal approach for repair of abdominal aortic aneurysms. Surg
Clin North Am 1989;69:795-806.