Use of an Artificial Neural Network for the Diagnosis of
Myocardial Infarction
William G. Baxt, MD
• Objective: To validate prospectively the use of an
artificial neural network to identify myocardial infarction
in patients presenting to an emergency department
with anterior chest pain.
• Design: Prospective, blinded testing.
• Setting: Tertiary university teaching center.
• Patients: A total of 331 consecutive adult patients
presenting with anterior chest pain.
• Measurements: Diagnostic sensitivity and speci-
ficity with regard to the diagnosis of acute myocardial
infarction.
• Main Results: An artificial neural network was
trained on clinical pattern sets retrospectively derived
from the cases of 351 patients hospitalized with a high
likelihood of having myocardial infarction. It was pro-
spectively tested on 331 consecutive patients present-
ing to an emergency department with anterior chest
pain. The ability of the network to distinguish patients
with from those without acute myocardial infarction
was compared with that of physicians caring for the
same patients. The physicians had a diagnostic sensi-
tivity of 77.7% (95% CI, 77.0% to 82.9%) and a diag-
nostic specificity of 84.7% (CI, 84.0% to 86.4%). The
artificial neural network had a sensitivity of 97.2% (CI,
97.2% to 97.5%; P = 0.033) and a specificity of 96.2%
(CI, 96.2% to 96.4%; P< 0.001).
• Conclusion: An artificial neural network trained to
identify myocardial infarction in adult patients present-
ing to an emergency department may be a valuable aid
to the clinical diagnosis of myocardial infarction; how-
ever, this possibility must be confirmed through pro-
spective testing on a larger patient sample.
Annals of Internal Medicine. 1991;115:843-848.
From the University of California, San Diego Medical Center,
San Diego, California. For the current author address, see end
of text.
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Jilectronic data processing technologies have been
used to aid in clinical diagnosis for more than 20 years
(1). The acceptance of such technologies has not oc-
curred (2). The reasons for this are varied but can be
traced to the fact that their use is time-consuming and
inconvenient and because most have not been able to
perform consistently better than physicians (2, 3). Arti-
ficial neural network-based pattern recognition has been
successfully used in several complex environments,
which suggests that this technology may, potentially, be
applied to the clinical setting (4-7). Unlike most other
forms of artificial intelligence, the artificial neural net-
work can improve performance by training. The net-
works can also define relationships among input data
that are inapparent using other approaches, and they
can use these relationships to improve accuracy. This
technology has been applied to the analysis of clinical
data (8-15); however, the network's diagnostic accuracy
has not been substantially better than that of physicians
(16-18).
An artificial neural network has been trained to diag-
nose, with a high degree of accuracy, acute myocardial
infarction in patients presenting to an emergency de-
partment (19). Data sets that were retrospectively ob-
tained from 356 patients suspected of having had a
myocardial infarction were used to train and test the
network. The network was trained on one half of the
patients and was tested on the remaining half to which
it had never been exposed. The process was reversed
and the results pooled in order to test all patients. The
network performed with a sensitivity of 92% and a
specificity of 96% (19). These figures were substantially
better than those reported previously for either physi-
cians (sensitivity, 88%; specificity, 71%) or any comput-
er-based technology (sensitivity, 88%; specificity, 74%)
(20). The network had a sensitivity of 80% and a spec-
ificity of 96% when all patients with electrocardio-
graphic evidence of myocardial infarction were removed
from the study sets. This work has recently been inde-
pendently corroborated (21).
Because the initial study was retrospective, the net-
work's performance must be prospectively validated be-
fore this network can be considered a legitimate aid to
clinical diagnosis. We report the results of the first
phase of this validation, the prospective testing of the
network on a group of 331 adult patients presenting to
an emergency department with anterior chest pain.
Methods
Description of Artificial Neural Network
An artificial neural network is a group of interconnected
mathematic equations that accept input data and that calculate
©1991 American College of Physicians 843
 an output based on this input. This structure is a predesigned
method for the application of nonlinear statistical techniques.
Network operation can be understood by referring to the
highly simplified artificial neural network depicted in Figure 1.
The input pattern in this instance consists of two variables, A
and B. Each of these variables is entered into the respective
input unit of the network. These values are multiplied by an
initially random number called a weight. The products of these
multiplications are summed and become the net input of the
hidden layer unit. This value is then entered in a logistic
function that calculates the activation of the hidden unit. The
activation of the hidden unit is multiplied by a third weight.
This product becomes the net input of the output unit. This
sum is then entered into the same logistic function that calcu-
lates the activation of the output unit or the ''network output."
The network is trained by modifying the value of the
weights. These values are modified through "back propaga-
tion," a process that uses the error in network output to
determine weight modification (5, 6). The error is defined as
the difference between the network output for a specific train-
ing pattern and the expected output of that training pattern.
During the training process, these weight values are deter-
mined so that the overall computation carried out by the net-
work is optimized to produce a minimal error. A properly
trained network is able to extract any functional or statistical
relationship between the input and output present in the train-
ing data.
Because of the large number of floating point calculations
made by the network, it must be run on a data processing
platform. The network can be hard-wired into the platform and
can reside as hardware or it can be written as a software
application. The network used in this study is illustrated in
Figure 2. It consists of 20 input units, two layers of 10 internal
or hidden units, and an output unit. The numbers of input
units, hidden units, and layers of hidden units were chosen by
trial and error during the initial development of the network
(19).
In applying the artificial neural network described here, the
inputs are selected from the presenting symptoms, the past
history findings, and the physical and laboratory findings of
Figure 1. Simplified operation of artificial neural network with
two input units, one hidden unit, and one output unit (2x1x1).
The input pattern consists of the two variables, A and B. Each
of these variables is entered into the respective input unit of
the network. These values are multiplied by an initially random
number called a weight [WT(1), WT(2)]. The products of these
multiplications are summed and become the net input of the
hidden layer unit. This value is placed in a logistic function
that calculates the net activation of the hidden unit. The net
activation of the hidden unit is multiplied by a third weight
[WT(3)]. This product then becomes the net input of the output
unit. This sum is entered into the same logistic function that
calculates the net activation of the output unit (termed network
output).
844 1 December 1991 • Annals of Internal Medicine • Volume 115 • Number 11
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Figure 2. Diagnostic network. 20x10x10x1 network with 20
input units, 2 layers of 10 units, and 1 output unit.
adult patients presenting to an emergency department with
anterior chest pain (Table 1). The network is trained so that
the output represents the presence or absence of acute myo-
cardial infarction. Although network output is not a probabil-
ity, it can be viewed in a similar manner, and output values
can be used as a measure of incident likelihood. To simplify
this initial prospective study, a cut-off value was chosen to
discriminate between the presence and absence of myocardial
infarction. In actual practice, the output could be viewed as
representing the likelihood of myocardial infarction.
Training the Network
The network training process consists of the retrospective
selection of a large number of patients who have presented
with anterior chest pain and who are known to have had or to
have not had an acute myocardial infarction. These patients'
cases are used to derive a set of training patterns for the
network. Training consists of the repeated sequential presen-
tation of the training set to the network until the error in the
output stops decreasing. Training is optimized by concurrently
testing the network on a subset of patterns derived from the
training patterns to which the network has not been exposed.
When the error made on this set has stopped decreasing,
training has been optimized.
The mathematics of this process have been previously re-
ported (6) and are presented in the Appendix. The artificial
neural network simulator for this project was written specifi-
cally for this study in C and was run on an 80386 microcom-
puter using an 80387 math coprocessor running at 20 mHz. The
network was trained as reported previously, using 351 of the
original 356 patients from the original study as the training set
(19). The five patients whose cases were omitted all had ex-
tremely atypical presentations. These cases were never re-
solved by the network. Previous analysis revealed that, by
omitting these cases, a weight set that made the network more
accurate in identifying prospective patients was derived. These
patients' confusing cases were, therefore, removed from the
training set to optimize network training.
Ten thousand iterations were run. The training parameters of
learning rate and momentum were set at 0.05 and 0.9, respec-
tively (see Appendix for an explanation). The final trained
weight set had an error rate of 0.00256 per pattern. Patients
whose pattern, when entered into the network, yielded an
output of more than 0.55 were deemed to have had a myocar-
dial infarction, and patients whose pattern resulted in an out-
put of 0.55 or more were deemed not to have had a myocardial
infarction. In this setting, the network output was between 0 to
0.1 and 0.9 to 1.0 97% of the time. The actual choice of cut-off
value—between 0.1 and 0.9—affects few cases. The value of
0.55 was chosen for this study because it segregated the pa-
tients best. When the trained network was tested on the train-
ing patterns, there were no diagnostic errors using the value of
 0.55 to discriminate between the presence and absence of Table 2. Accuracyy of the Ph ysician and of th e Artificial
myocardial infarction. In the initial study (19), the network was Neural Network iin Diagnosinig Acute Myocarclial Infarc-
trained on half of the 351 patients and then was tested on the
second half to which it had not been exposed. This process tion
was then reversed so that the network could be tested on all
351 patients. In this instance, all 351 patients participating in Variable Data 95% CI P Value
the initial study were used as the training set (19). %
All patients 18 years of age or older presenting to an emer-
gency department with anterior chest pain were enlisted in the Sensitivity
study. The physician treating the patient was asked to com- Physicians
plete a questionnaire that documented the presence of the Correct, n 28
items listed in Table 1. In this way, all data used by the Incorrect, n 8
network were coded by the physicians caring for the patients, Percentage 77.7 77.0 to 82.9
and both the network and the physician used the same data as Network
the basis for diagnosis. To test the network in a setting as Correct, n 35
close as possible to the environment in which it would operate Incorrect, n 1
prospectively, it was tested only on the inputs provided by the Percentage 97.2 97.2 to 97.5 0.03
treating physicians. No attempt was made to change what, on Specificity
retrospective chart review, turned out to be inaccurate or Physicians
incorrect inputs made by these physicians. The physician was Correct, n 250
also asked to guess whether the patient had had a myocardial Incorrect, n 45
infarction. The physicians were medical residents in postgrad- Percentage 84.7 84.0 to 86.4
uate years 2 and 3 and emergency department attending faculty Network
physicians. Correct, n 284
Final patient diagnosis was established by the following: Incorrect, n 11
Admitted patients were followed through review of their inpa- Percentage 96.2 96.2 to 96.4 < 0.001
tient record after discharge. Patients who were referred to the
outpatient department were followed through review of their
outpatient records. Patients who were neither admitted nor
referred to the outpatient center were followed through tele- ues of less than 0.05 were considered statistically significant.
phone interview 3 weeks after their initial emergency depart- Power was calculated by use of standard power formulas.
ment visit. Patients who could not be followed were dropped
from the study. The follow-up data were entered into the data
base without reference to the presenting data so that this Results
process would be blinded to the initial data entry.
Myocardial infarction was defined in this study as fulfillment The cases of 355 patients were initially studied.
of one of the following criteria (20): characteristic evolution of Twenty-four nonadmitted patients could not be fol-
serum enzyme levels, including a creatine kinase MB fraction lowed. These 24 patients had noncardiac diagnoses, and
of at least 5% of the total creatine kinase or a lactate dehy- normal electrocardiograms were obtained for these pa-
drogenase isoenzyme 1 level that was higher than the isoen-
zyme 2 level (in the absence of hemolysis or renal infarction); tients in the emergency department. Of the study pa-
an electrocardiogram showing the development of new patho- tients, 192 were men (mean age, 51.6 years) and 139
logic Q waves (lasting at least 0.04 seconds) and at least a 25% were women (mean age, 52.4 years). Thirty-six patients
decrease in the amplitude of the following R wave, as com- had had a myocardial infarction, 63 patients had cre-
pared with that of the electrocardiogram obtained in the emer- scendo angina, 38 patients had angina, and the remain-
gency department; or a scintiscan showing the focal uptake of
tech-99m stannous pyrophosphate in the cardiac area if the ing 194 patients had noncardiac etiologies. No patient
serum enzyme level peaked before hospitalization. In addition, diagnosed with myocardial infarction did not fulfill the
all records were reviewed to determine whether the cases of all original study criteria.
patients diagnosed as having had a myocardial infarction met Network testing of all 331 patients yielded 0.03773
the study definition. Statistical analysis was carried out by the
calculation of confidence intervals (22) and by use of chi- error per patient. Table 2 depicts the diagnostic perfor-
square analysis of 2-by-2 contingency tables using the Yates mances of the physicians and of the artificial neural
correction and the McNemar symmetry chi-square test. P val- network. The physicians correctly diagnosed 28 patients

Table 1. Input Variables

History History Examination Electrocardiographic

Findings Findings Findings

Age*t Acute myocardial Jugular venous 2-mm ST-segment elevation*

infarction* distension*
Sex* Angina* Rales* 1-mm ST-segment elevation*
Left anterior location of pain* Diabetes* ST-segment depression*
Intensity of pain Hypertension* T-wave inversion*
Radiation of pain Significant ischemic change*
Nausea and vomiting*
Diaphoresis*
Syncope
Shortness of breath*
Palpitations*
Response to nitroglycerin*

* Variables actually used by the network.

t Analog coded.

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 with myocardial infarction for a sensitivity of 77.7%
(95% CI, 77.0% to 82.9%) and correctly diagnosed 250
patients without myocardial infarction for a specificity
of 84.7% (CI, 84.0% to 86.4%). The network incorrectly
diagnosed 1 patient with myocardial infarction for a
97.2% sensitivity (CI, 97.2% to 97.5%) and incorrectly
diagnosed 11 patients without myocardial infarction for
a specificity of 96.2% (CI, 96.2% to 96.4%). The differ-
ence in the sensitivity had a chi-square Yates-corrected
P value of 0.033 and a McNemar symmetry chi-square
P value of 0.008. The difference in specificity had a
Yates-corrected chi-square P value of less than 0.001
and a McNemar symmetry chi-square P value of less
than 0.001.
The charts of all patients whom the network incor-
rectly diagnosed were analyzed. Eleven patients were
incorrectly diagnosed as having had a myocardial in-
farction. Of these, 4 patients were recorded as having
had new ischemic changes on their electrocardiograms:
1 with new 2 mm of ST-segment elevation, 2 with new
1 mm of ST-segment elevation, and 1 with new T-wave
inversion. When the electrocardiograms of these pa-
tients were reviewed by inpatient services, all four were
thought not to have had new ischemic changes. The 1
patient who was incorrectly diagnosed as not having
had a myocardial infarction had no significant clinical
findings other than minimal left anterior chest pain. This
patient had no electrocardiographic evidence of acute
myocardial infarction, and this patient's final diagnosis
was based on enzyme changes alone.
Discussion
The diagnostic accuracy of the artificial neural net-
work in predicting both the presence and the absence of
acute myocardial infarction in a group of prospectively
collected patients to whom the network had never been
exposed was better than that of the physicians caring
for these patients in the emergency department. Artifi-
cial neural network technology was applied to clinical
data in the hope that diagnostic accuracy could be im-
proved by using information or relationships among
clinical pattern sets that were inapparent using other
means. Although the evidence for this is indirect, the
better diagnostic accuracy of the network suggests that
it may identify such relationships in the clinical data
sets that have heretofore not been elucidated.
Another possible reason for the improved accuracy of
the network is that this paradigm, in contrast to other
computer-based approaches, can operate with inaccu-
rate or missing data. Such networks are known to be
able to identify relationships even when some of the
input data are incomplete or inaccurate (12). This fea-
ture makes the network an excellent candidate to deal
with the inaccuracy and inconsistency associated with
patient histories and physical findings. Further, the net-
work appears to be able to deal with the complexities of
singular disease states characterized by totally differing
clinical presentations.
The artificial neural network may achieve higher ac-
curacy than the other two widely used approaches to
the diagnosis of myocardial infarction, regression anal-
ysis (23) and recursive partitioning (20), because these
846 1 December 1991 • Annals of Internal Medicine • Volume 115 • Number 11
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are linear statistical methodologies. The artificial neural
network is a method for the application of nonlinear
statistics. Although it can only be postulated, the ability
of the network to identify new relationships between
input clinical variables may emanate from its inherent
nonlinear method of data analysis.
The diagnostic accuracy afforded by the use of an
artificial neural network could significantly affect the
clinical diagnosis of myocardial infarction. The im-
provement in sensitivity could potentially lead to an
improved ability to identify those patients with actual
myocardial infarction. Missed diagnoses of myocardial
infarction have been reported to be the single largest
cause of the loss of medical malpractice settlements
made against emergency departments (24). Further, the
high specificity that results from network use could lead
to significant cost savings by reducing the unnecessary
admission of patients to either the intensive care unit or
the hospital. One study estimated that a 3% improve-
ment in specificity could lead to an annual national cost
savings of $85 million (19). The improvement in speci-
ficity by at least 10%, as shown in this study, could
yield a potential annual savings of over $0.28 billion.
Actual application of this technology would not be dif-
ficult. Once the network is trained, it could be placed in
a hand-held calculator and could provide immediate
outputs for inputted sets of clinical variables.
The interpretation of these results is limited in several
ways: Not all patients were followed diagnostically in
the same manner. Neither serial cardiac enzyme level
measurements nor electrocardiograms were obtained for
patients not admitted to the hospital. Twenty-four pa-
tients could not be followed and were dropped from the
study; however, all of these patients were thought to
have chest pain of noncardiac etiology, and normal
electrocardiograms were obtained for these patients in
the emergency department. If these patients were in-
cluded in the study and were considered to have been
correctly diagnosed as not having had a myocardial
infarction by the physicians, physician specificity would
improve to 85.89%, and physicians would still be sig-
nificantly less accurate than the network.
The network was tested against the physicians caring
for the study patients, and its performance was not
compared with that of other previously developed elec-
tronic aids to the diagnosis of myocardial infarction (20,
23). The sensitivity and specificity observed for physi-
cians in this study differed significantly from those pre-
viously reported for a considerably larger number of
physicians (20), the sensitivity reported here being
lower (77% compared with 88%) and the specificity
being higher (85% compared with 71%). The former
weighted the statistical analysis in favor of the rejection
of the null hypotheses in terms of the reported differ-
ences in sensitivities. If physician sensitivity is 88%, as
previously reported, then a minimum of 100 patients
who have had an acute myocardial infarction or a total
of 1100 patients must be enlisted to reach statistical
significance (Yates-corrected chi-square, P - 0.032). In
addition, the physician sensitivity and specificity in this
study was measured from the actual physician guess
about the presence or absence of myocardial infarction,
 whereas that with which it is compared was based on
triage decisions made by the treating physicians (20).
Finally, only the diagnosis of myocardial infarction
was studied, whereas the diagnosis of other important
cardiac conditions, such as new-onset angina or cre-
scendo angina, was not studied. This limitation simpli-
fied the study and the interpretation of results. Clearly,
if this technology proves to be as accurate as these
initial data imply, the technology could be extended to
other ischemic conditions.
Until the network is tested on a large number of
patients, the study can be seen only as a first step in the
prospective validation of the use of the artificial neural
network as an aid to the clinical diagnosis of myocardial
infarction. A multicenter study designed to compare
prospectively the performance of the artificial neural
network with those of physicians and other technologies
on a large number of patients is currently underway (20,
23). If this study is successful, the possibility that this
technology could be used prospectively as well as be
extended to other clinical settings could be explored.
Finally, potentially one of the most important aspects
of these findings may be that the network may be able
to identify relationships between clinical patient varia-
bles that have not been appreciated by clinicians in the
past. Strategies have already been developed to define
these relationships (21, 25). Not only does this possibil-
ity have important implications about the limits of clin-
ical reasoning, but it also may suggest that such tech-
nologies as reported here may potentially be used in
further elucidating disease processes in general. Such
conclusions await ultimate validation of these observa-
tions and the successful extension of these technologies
to other disease states.
Acknowledgments: The author thanks Dr. David Zipser for technical
help and Ms. Kathleen James for manuscript preparation.
Requests for Reprints: William G. Baxt, MD, Department of Emer-
gency Medicine, UCSD Medical Center, 225 Dickinson Street, #8676,
San Diego, CA 92103-8676.
Current Author Address: Dr. Baxt: Department of Emergency Medi-
cine, UCSD Medical Center, 225 Dickinson Street, #8676, San Diego,
CA 92103-8676.
Appendix
The mathematical operation of the network can best be
appreciated by again referring to Figure 1. This aspect of
network application is independent of its specific use and can
be viewed as generic. The network functions by the application
of binary or analog coded data comprising the pattern set to
the 20 input units (see Table 1). This signal is then multiplied
by the initially random weights on the projections between
each input unit and the first layer hidden units:
n diagnosis. Ann Intern Med. 1988;108:80-7.
1. netpi = ZJ wuapj + biasj
j=o
where netpi equals the net input of the unit for pattern p, w is
a random weight, a is the input value applied to the unit, j
represents the input or presynaptic units, / represents the first
layer hidden unit or postsynaptic unit, and bias is a modifiable
weight that is multiplied by an input that is always equal to 1.
The net activation of the hidden unit is calculated by:
1 6. McClelland JL, Rumelhart DE. Training hidden units. In: McClel-
2 a [ =
' P J + e~netpi
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The activation of the second layer hidden units is calculated
by use of the first equation in a manner analogous to that used
to calculate the activation of the first layer hidden units. In the
latter instance, the input signal now becomes the net activation
of each first layer hidden unit, which is multiplied by the
weights on the projections between each of the first and sec-
ond layer hidden units. Unit activation is calculated by the use
of equation 2. Network output is also calculated in an analo-
gous manner, with the second layer hidden units now provid-
ing the input signal, which is multiplied by the weights on the
ten projections to the output unit. Unit activation (network
output) is again calculated by use of equation 2.
The difference between a training pattern output or target
value and the network output api, termed e, is calculated by
subtracting network output from the target value tpi. An e is
calculated for each noninput unit of the network and used by
the back propagation algorithm to modify all weights of the
network such that, when pattern p is again inputted, the dif-
ference between network output and the pattern target value
will diminish.
Weight is modified by the derivation of delta. The delta for
the output unit is calculated by:
3. dp, = (tpi - api)fi(netpi)
where fi(netpi) is the derivative of the activation function with
respect to a change in the net input to the unit.
The delta for the hidden units is calculated in terms of the
units to which they project and the weights on those projec-
tions:
n
4. SPi=fi(netpi) 2 SpkWki
k= Q
Weights and biases are updated by the calculation of the
delta weight:
5. Awj = awj + ((1 - a)(e8jaj))
where alpha is termed network momentum and epsilon is
termed the learning rate parameter. Weights are updated by
adding the delta weight to the old weight.
Training of the network is followed by calculating the
summed square of the error, represented by E, across the
entire pattern set:
6. E = E E (tPi ~ Opi)2
P i
where the index p ranges over the set of input patterns P, i
ranges over the set of output units, tpi is the target of pattern
p, Opi is the network output for pattern p. When the summed
square of the error has ceased diminishing or has reached 0,
the network has been trained. If no relationship between the
pattern sets and their target value exists, this value will not
diminish.
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