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Correct Utilization of Exercise
Electrocardiographic Leads in
Differentiation of Men With Coronary
Artery Disease from Patients With a Low
Likelihood of Coronary Artery Disease
Using Peak Exercise ST-Segment
Depression
Jari Viik,
LicTech,
Rami Lehtinen, PhD, Väinö Turjanmaa,
Jaakko Malmivuo, PhD
MD,
Kari Niemelä,
MD,
and
In this study we compared the diagnostic characteristics
of the individual exercise electrocardiographic leads, 3
different lead sets comprising standard leads and the
effect of the partition value in the detection of coronary
artery disease (CAD). The diagnostic variable used was
ST-segment depression at peak exercise, and the study
population consisted of 101 patients with CAD and 100
patients with a low likelihood of the disease. The lead
system used was the Mason-Likar modification of the
standard 12-lead system and exercise tests were performed on a bicycle ergometer. The comparisons were
performed by means of receiver-operating characteristic
analysis and by determining sensitivities at a fixed 95%
specificity. These properties, defined here as diagnostic
capacity, were the most efficacious in leads I, 2aVR, V4,
V5, and V6. Diagnostic capacities in leads aVL, aVF, III,
V1, and V2 were quite poor; statistical comparisons
indicated significant differences between these leads
and lead V5 (p <0.0001 in each case). Use of the
maximum value of ST-segment depression at peak ex-
ercise derived from all 12 leads produced a considerable decrease in the diagnostic capacity of the exercise
electrocardiogram compared with lead V5. The exclusion of leads aVL, V1, and III improved the diagnostic
capacity compared with the 12-lead set, but it was still
smaller than that of lead V5. With use of a lead set with
the 5 best leads increased the diagnostic capacity over
other lead sets and over any individual lead. Further
improvement was noted when a 50% smaller partition
value was applied to leads I and 2aVR than for the
other leads (p 5 0.041). In conclusion, this study suggests that use of leads I, 2aVR, V4, V5, and V6 is the
most influential when differentiating between patients
with CAD and patients with a low likelihood of disease
using peak exercise ST-segment depression. The effective use of leads I and 2aVR requires the partition value
applied for these leads to be 50% smaller than that used
for the lateral precordial leads. Q1998 by Excerpta
Medica, Inc.
(Am J Cardiol 1998;81:964 –969)
y convention, a fixed partition value for ST-segment depression (0.10 mV) is recommended for
B
the detection of coronary artery disease (CAD) in each
for screening. On the contrary, the specificity of the
test should be kept as high as possible to avoid additional unnecessary further examinations. This study
compares the diagnostic characteristics of the individual exercise ECG leads of the standard 12-lead system
in differentiating male patients with CAD from patients with a low likelihood of the disease. Furthermore, the objectives were also to evaluate the importance of the number of leads when using the maximum
ST-segment depression value derived from 3 different
lead sets and to specify the partition value applied for
individual leads.
lead,1–3 despite the different diagnostic characteristics
of the individual leads.4 – 6 With use of this approach,
it is apparent that the number of true-positive responses increases when more leads are used, but at the
same time the number of false-positive responses also
increases. Considering the usefulness of the exercise
test, 100% sensitivity is not essential, especially when
the exercise electrocardiographic (ECG) test is used
From the Ragnar Granit Institute, Tampere University of Technology;
Department of Clinical Physiology and Division of Cardiology, Department of Internal Medicine, Tampere University Hospital and Medical
School, University of Tampere, Tampere, Finland. This work was
supported in part by the Academy of Finland, the Emil Aaltonen
Foundation, the Finnish Cultural Foundation (Pirkanmaa Fund), the
Ragnar Granit Foundation, the Tampere Science Foundation, and the
Wihuri Foundation. Manuscript received July 28, 1997; revised
manuscript received and accepted January 2, 1998.
Address for reprints: Jari Viik, LicTech, Ragnar Granit Institute,
Tampere University of Technology, P.O. Box 692, FIN-33101 Finland.
964
©1998 by Excerpta Medica, Inc.
All rights reserved.
METHODS
Study population: Subjects were selected from a
group of 1,507 consecutive patients who underwent
routine clinical exercise testing. All patients had been
referred for exercise testing at Tampere University
Hospital, Finland, and there were no volunteer subjects. All patients selected were men. Patients with left
or right bundle branch block and recent myocardial
infarction (,8 weeks) were excluded.
0002-9149/98/$19.00
PII S0002-9149(98)00073-3
TABLE I Clinical Characteristics of Study Population
Characteristic
All Patients
(n 5 201)
CAD
(n 5 101)
Reference
(n 5 100)
50 6 11
144 6 50
145 6 27
54 6 8
113 6 35
126 6 21
46 6 13*
175 6 44*
164 6 19*
Electrocardiographic leads, lead
sets, and partition values used in the
analysis: All individual leads of the
12-lead system were used separately
in the detection of ischemic responses. Lead aVR was inverted so
that it had a lead vector directed to
the left and downward. Thus, a pos136
38
98*
itive response to the exercise test
51
51
0*
14
12
2
also corresponded to ST-segment de40
40
0*
pression. The importance of the
number of leads was studied with 3
83
83
0*
different lead sets. The maximum
3
3
0
STpeak value, determined from the
66
66
0*
34
34
0*
leads of each lead set, was used as
the diagnostic classifier. The 3 lead
*p ,0.0001.
sets used (1) all 12 leads, (2) 9 leads
Values for age, maximal workload, and maximum heart rate are mean 6 SD. CAD 5 coronary artery
disease; MI 5 myocardial infarction.
(aVL, III and V1 were excluded), and
(3) 5 leads (I, 2aVR, V4, V5, and
V6) of the standard 12-lead electroThe CAD group was selected from patients who cardiogram, and were denoted by A12, A9, and A5,
underwent selective coronary angiography (performed respectively. Selection of the leads for leads sets A9
using the Judkins technique) within 180 days of exercise and A5 was based on the diagnostic capacities of the
testing. In all cases, each coronary artery was imaged in individual leads. Different partition values were apmultiple views. The degree of stenosis was defined as the plied for the particular leads in order to define the
greatest percent reduction in luminal diameter in any effect of more detailed criteria on the sensitivity and
view compared with the nearest normal segment. CAD specificity of the test.
was considered significant when $50% luminal narrowData analysis and statistical methods: Continuous
ing of the diameter of the major epicardial coronary variables are described as mean 6 SD. Significant
arteries was present. After these exclusions there were differences among study groups with respect to
101 men included in the CAD group. Of these, 44 had cardiac medication, chest pain, and previous myosignificant stenosis in all 3 major coronary arteries or in cardial infarction were examined using the chithe left main coronary artery, 25 had 2-vessel disease, square test with Yates’ correction. Quantitative
and 32 had 1-vessel disease.
variables were analyzed using a 2-tailed Student’s t
The reference group was selected on the basis of test. Comparisons of the sensitivity of individual
previous clinical history. The inclusion criteria for the leads and different lead sets at a fixed 95% specireference group were no history of any cardiac dis- ficity were performed using McNemar’s modificaease, a normal resting electrocardiogram, and no an- tion of the chi-square method for paired proporginal type chest pain or cardiac medication. After tions. Due to the fact that the sensitivity and specthese restrictions, 100 male patients were available for ificity are dependent on the partition values chosen
use in the study. With probabilistic assessment, the for test positivity, the diagnostic accuracy of the
reference group was estimated to have a low likeli- study variables without any partition value were
hood (p ,0.05) of CAD.7
also compared by means of receiver-operating charExercise electrocardiographic test: The exercise test acteristic (ROC) analysis. The area under the ROC
was performed on a bicycle ergometer using a com- curve represents the overall diagnostic perforputerized recording system (SYSTEM II EXES, Si- mance, i.e., the probability that a random pair of
emens-Elema, Solna, Sweden). The graded protocol patients with and without CAD will be correctly
followed a standard clinical routine with an initial diagnosed.12 Statistical differences between the arworkload of 50 W and an increment of 50 W every 4 eas under 2 ROC curves were compared using a
minutes. The exercise tests were sign- and symptom- nonparametric analysis of correlated ROC curves13
limited maximal tests using recommended criteria for with a routine written by Vida14 (version 2.5). In
termination8; fatigue and chest pain were the reason statistical comparisons, individual leads were comfor termination in most cases. The lead system used pared with lead V5. Lead sets A12, A9, and A5 were
was the Mason-Likar modification of the standard compared with each other and with lead V5. When
12-lead system.9 Computer-determined ST-segment defining the alpha level of the tests, the Bonferoni
amplitudes measured to the nearest 10 mV were ob- correction was taken into account in all statistical
tained at a point 60 ms after the J junction,10,11 with comparisons.15
the end of the PR segment considered as the isoelectric line. The ST-segment amplitude, heart rate, and RESULTS
workload data were stored for further processing and
Group characteristics and exercise performance:
analysis. The ST-segment value at the peak exercise Group characteristics and statistical differences ac(STpeak) was used as a diagnostic classifier.
cording to clinical status are listed in Table I. Because
Age (yr)
Maximal workload (W)
Maximum heart rate (beats/min)
Chest pain description
No chest pain
Typical chest pain
Atypical chest pain
History of previous MI
Medication
b blockers
Digitalis
Nitrate preparation
Calcium antagonist
CORONARY ARTERY DISEASE/CORRECT USE OF ST–SEGMENT DEPRESSION
965
FIGURE 1. Standard deviations (SD), standard errors (SE) and means of the ST-segment values at peak exercise lead by lead. Shaded
symbols indicate the CAD group and open symbols patients with a low likelihood of the disease. STpeak 5 ST-segment value at peak
exercise.
of the different exclusion criteria used in the selection
of the groups, highly significant differences (p
,0.0001) were achieved with respect to age, maximal
workload, maximum heart rate, chest pain, previous
myocardial infarction, and cardiac medication, with
the exception of digitalis.
Individual leads: The descriptive statistics (mean,
SE, and SD) of the STpeak in each lead are shown in
Figure 1. The order of the limb leads is in accordance
with lead direction in the frontal view. The STpeak
values of the CAD group and the reference group are
illustrated side by side, starting with the CAD group.
The mean values of STpeak were lower in the CAD
group than in the reference group in each lead, with
the exception of lead V1.
The ROC curves for each individual lead are shown
in Figure 2. The circles indicate 20.10 mV STpeak (1.0
mm ST-segment depression) and the diamonds indicate
the nearest partition values providing 95% specificity.
The value of ,0.500 in lead V1 indicated that lead V1
should have been inverted in this study population (the
ROC area for 2V1 would be 0.577). Statistical comparison of the leads showed that the areas under the ROC
curves in leads aVL, aVF, III, V1, and V2 were significantly smaller than in lead V5 (p #0.0001 in all cases).
With use of a corrected alpha level of 0.0045 for the
univariate Z test, significant differences were not observed between the ROC curves of leads V5 and II (p 5
0.0395) and between the ROC curves of leads V5 and V3
(p 5 0.0047). Moreover, no significant differences were
detected when comparing leads I, 2aVR, V4, and V6
with lead V5.
The sensitivity values obtained at 95% specificity
showed statistical differences when comparing leads
III, aVL, aVF, V1, and V2 with lead V5 (in all cases
p , 0.0001), lead II with V5 (p 5 0.0004) and lead V3
with V5 (p 5 0.0007), but not in the case of leads I,
2aVR, V4, and V6.
966 THE AMERICAN JOURNAL OF CARDIOLOGYT
VOL. 81
Lead sets: The ROC curves determined using the
maximum values from lead sets A12, A9, and A5 are
shown in Figure 3. The circles indicate 20.10 mV
STpeak and the diamonds indicate the nearest partition
values providing 95% specificity. By comparing the
areas under the ROC curves, significant differences
(alpha level of 0.017) were found between A5 and A9
(p 5 0.0152), A5 and A12 (p ,0.0001), and A9 and
A12 (p 5 0.0001). When comparing the different lead
sets with lead V5, a significant difference was only
observed in the case of V5 and A12 (p 5 0.0023). No
significant differences were observed between A5 and
V5 (p 5 0.0906) or V5 and A9 (p 5 0.4181).
By comparing the sensitivities at fixed specificity between lead sets, significant differences (alpha
level of 0.017) were detected between A5 and A12
(p ,0.0001), A5 and A9 (p 5 0.0060), and A9 and
A12 (p 5 0.0008). A significant difference was also
found when comparisons were performed between
lead set A5 and lead V5 (p 5 0.0133) and between
V5 and A12 (p 5 0.0003), but no significant difference was observed between V5 and A9 (p 5
0.4227). The partition values corresponding to a
specificity of 95% were dissimilar. The partition
value decreased proportionally when the number of
leads in the set decreased (from 20.14 mV to
20.06 mV).
The specificity and sensitivity values of lead sets
A12, A9, and A5 at different partition values are
shown in Figure 4 and are denoted by A to D. For
cases A and C the specificity and sensitivity values
were determined using different partition values for
leads I and 2aVR (first value in the positive test
criteria keybox) and for the other leads (second value);
for example, for cases labeled C in Figure 4, a partition value of 20.05 mV for test positivity was applied
to leads I and 2aVR and a partition value of 20.10
mV was applied to the other leads. The distribution of
APRIL 15, 1998
FIGURE 3. Receiver-operating characteristic curves for 3 different
lead sets using the maximal ST-segment values at peak exercise
derived from each lead set. Values adjacent to the name of the
lead set indicate the areas under the receiver-operating characteristic curves. Circles indicate a value of 0.10 mV ST-segment
depression and diamonds indicate the nearest partition value at
95% specificity. A12 5 all the leads of 12-lead system; A9 5
aVL, III, and V1 excluded; A5 5 leads I, –aVR, V4, V5, and V6.
DISCUSSION
FIGURE 2. Receiver-operating characteristic curves for each individual lead of the 12-lead system using ST-segment values at
peak exercise. Values adjacent to the name of the lead indicate
the areas under the receiver-operating characteristic curves. Circles indicate a value of 0.10 mV ST-segment depression and diamonds indicate the nearest partition value at 95% specificity.
the STpeak values in each lead in the CAD group and
reference group (SD in Figure 1) was taken into account when defining lead specific partition values.
Using the 20.05 mV criterion for leads I and 2aVR,
the sensitivity improved by 5 percentage points. Further improvement in sensitivity was achieved when
the partition value for test positivity was reduced, but
at the same time the specificity of the test decreased.
This decrease in specificity was smaller in lead set A5
than in lead sets A9 or A12. The specificity of the lead
sets at different partition values indicated that lead set
A5 was superior to lead sets A9 and A12. Comparing
the traditional criterion D (STpeak from all leads
#20.10 mV) and criterion C (STI,2AVR #20.05 mV
or STother #20.10 mV), a significant difference was
observed in lead set A5 (p 5 0.0412).
Individual leads: Many studies16 –19 have shown
lead V5 to be capable of detecting most ischemic
responses when a positive test criteria of $0.10 mV
ST-segment depression is used. According to this
study a fixed global partition value applied to each
standard lead does not treat individual leads equally.
Figure 1 shows that it is easy to see that larger partition values are most suitable for the lateral precordial
leads (V4, V5, and V6). The highest sensitivities at a
partition value of 20.10 mV were found in leads V5
and V6 (Figure 2), supporting the previous statement.
Using the same 20.10 mV criterion, leads I and
2aVR attained extremely poor sensitivities. A model
study20 and our previous clinical study21 also support
these findings. However, the areas under ROC curves
of these leads indicated diagnostic performances
equally as good as those of the lateral precordial leads,
and the sensitivities at a fixed 95% specificity did not
significantly differ from lead V5. The only difference
is that the partition value for these leads should be
50% smaller.
Considering the diagnostic capacity of individual
leads, the results of this study support incontestably
the previous finding6,21 that leads aVL and V1 are
unreliable in the general detection of CAD. The areas
under the ROC curves were ,0.600 and the sensitivities at 95% specificities were the most unsatisfactory.
Additionally, the diagnostic capacities of leads aVF,
III, and V2 were also deficient and significantly
smaller than in lead V5.
Multiple leads: Several studies have demonstrated
an improvement in the detection of CAD using multiple leads during the exercise test.16,22–26 Increasing
CORONARY ARTERY DISEASE/CORRECT USE OF ST–SEGMENT DEPRESSION
967
Partition value: Comparison of lead
sets A5, A9, and A12, with particular
positive test criteria revealed the comparatively poor performance of lead set
A12 in distinguishing patients with
CAD from patients with a low likelihood of the disease (Figure 4). When
the number of leads included in the
analysis was reduced, the specificity at
a fixed positive test criterion increased
without significant reduction in sensitivity. On the other hand, the sensitivity increased in each lead set when the
50% smaller (20.05 mV) partition
value was used for leads I and 2aVR,
without a reduction in specificity. The
results distinctly demonstrated that
more efficient use of leads I and 2aVR
in CAD detection requires lower partition values for those leads. By decreasing positive test criteria to 20.03 mV
for leads I and 2aVR and to 20.06
mV for the other leads, a further improvement in sensitivity was achieved,
but at the same time the specificity of
the lead sets diminished. In lead sets
FIGURE 4. The sensitivity and specificity values of 3 different lead sets using the
A9 and A12, the reduction in specificST-segment values at peak exercise from each lead set. Points A to D illustrate the
ity was the same as the increase in
specificity and sensitivity values for different positive test criteria. The first criterion
in A and C is for leads I and –aVR and the second criterion for the remaining leads
sensitivity. In lead set A5 the increase
(for example in case C, a partition value of – 0.05 mV for test positivity was apin sensitivity was double the reduction
plied to leads I and –aVR and a criterion of – 0.10 mV was applied to the other
in specificity. This indicated that lead
leads). Abbreviated lead sets names are the same as in Figure 3.
set A5 was not so susceptible to falsepositive responses as the other lead
sets.
the number of leads used in the analysis of ischemic
Study limitation: There are several limitations to
response detection increases the sensitivity, but often this study. The study population was restricted to men.
a problem arises due to an increase in false-positive Thus, the conclusions may not be directly applicable
responses, and the diagnostic accuracy of the lead set to women. The CAD patients had angiographically
does not necessary increase. When using the maxi- proven CAD, but the reference patients were defined
mum value from all 12 leads (lead set A12) in the only by clinical history. In an ideal study, the entire
analysis of CAD detection, the diagnostic capacity of study population would have been examined by anthe STpeak diminished compared with lead V5 or lead giography. However, taking into account the more
sets A9 and A5. When using the same fixed partition frequent use of exercise ECG testing as a screening
value for different lead sets (e.g., 20.10 mV in Figure test in large populations, this type of approach with a
3), it can be seen that the deterioration in diagnostic bipartite study population is appropriate. Cardiac
capacity was caused by a decrease in specificity (the medication, the type of exercise test, and the protocol
sensitivity did not change). Thus, use of a larger influenced the results. However, these influences can
be assumed to be identical for each lead and thus the
partition value (from 20.06 mV to 20.14 mV) is
comparative performance of different leads would be
recommended if high specificity is desired. The ex- the same regardless of medication, exercise modality,
clusion of the poorest leads (aVL, III, and V1) from or protocol.
the analysis increased the area under the ROC curve as
well as the sensitivity at 95% specificity, but still the
Acknowledgment: We thank Simon Walker, PhD,
diagnostic capacity of lead set A9 was approximately and James Rowland for their valuable suggestions and
the same as the diagnostic capacity of the best indi- assisting in preparation of this manuscript.
vidual leads. This study indicated that the use of lead
set A5 improved the diagnostic capacity of the STpeak
significantly compared with lead sets A9 and A12.
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