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Transcript
542
Diagnostic Value of QRST Isointegral Maps in
Detecting Myocardial Infarction Complicated
by Bundle Branch Block
Hiroshi Hayashi, MD, Shinji Watabe, MD, Seitaro Yabe, MD, Kazuhide Takami, MD,
Shigeki Ohsugi, MD, Makoto Hirai, MD, Makiko Mizutani, MT, Hidehiko Saito, MD
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
The clinical usefulness of QRST isointegral maps (IQRST map) for detecting myocardial infarction
that was complicated by intraventricular conduction disturbances was evaluated in patients with
right bundle branch block (group RBBB, 64 patients) and left bundle branch block (group LBBB,
40 patients) by comparison with the normal mean IQRST map derived from 50 normal subjects.
Myocardial infarction complicated the conduction disturbances in 24 of the 64 RBBB and in 18
of the 40 LBBB patients. A correlation coefficient was used for assessing the similarity of each map
pattern with the normal mean IQRST map. The difference map was made by subtracting the
average normal IQRST map from each abnormal IQRST map, and those differences that were less
than 2 SD from the mean were retained as a significant area. The number of leads and their sum
of differences were used to represent the size of the difference map. Correlation coefficients were
significantly (p<0.001) smaller in patients with bundle branch block complicated by myocardial
infarction than in patients with conduction disturbances not complicated by myocardial infarction. A significant area emerged in the difference map in all patients with myocardial infarction
complicated by conduction disturbances. The emergence of a significant area revealed high
diagnostic accuracy for detecting myocardial infarction in group RBBB (89.1%). The size of a
significant area in a difference map was significantly larger in cases with complicated myocardial
infarction than in cases with uncomplicated myocardial infarction in either group RBBB or group
LBBB (p<0.001). The determination of the critical size of a significant area obtained by
discriminant analysis improved the diagnostic accuracy of detecting complicated myocardial
infarction to 98.4% and 87.5% for groups RBBB and LBBB, respectively. The IQRST map was
highly useful for detecting myocardial infarction masked by intraventricular conduction
disturbances. (Circulation 1989;80:542-550)
In patients with myocardial infarction complicated by bundle branch block or other intraventricular conduction disturbances, the diagnostic features for detecting myocardial infarction
are often hidden in the wide QRS complex.1 Even
though many investigators have attempted to diagnose myocardial infarction correctly in the presence
of bundle branch block, correct diagnosis is still
often difficult by standard 12-lead electrocardiogram (ECG).2-7 Also, one study has attempted to
diagnose myocardial infarction by the direction and
magnitude of the spatial ventricular gradient derived
from the vectorcardiogram.8 However, the diagnostic accuracy of this method remains unsatisfactory.8
From the First Department of Internal Medicine, Nagoya
University School of Medicine, Showaku, Nagoya, Japan.
Address for correspondence: Hiroshi Hayashi, MD, First
Department of Internal Medicine, Nagoya University School of
Medicine, 65 Tsurumaicho, Showaku, Nagoya, 466, Japan.
Received September 2, 1988; revision accepted May 9, 1989.
The present study examined the clinical usefulness of QRST isointegral maps (IQRST map9-12) based
on Wilson's concept of the ventricular gradient13 for
diagnosing myocardial infarction complicated by
bundle branch block.
Methods
Patients
Patients who had either complete right bundle
branch block (RBBB) or complete left bundle
branch block (LBBB) according to routine electrocardiograms and who visited our hospital
between January 1983 and August 1987 were
included in the present study if 1) a medical
history was obtained satisfactorily and 2) except
for myocardial infarction, there was no obvious
underlying heart diseases such as congenital or
valvular heart disease, hypertensive cardiovascular disease, and primary myocardial disease as
Hayashi et al Isointegral Maps
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
assessed by routine examinations including echocardiography and Doppler cardiography.
Sixty-four patients had RBBB, and 40 had LBBB.
Of the 64 patients with RBBB, 40 (26 men, 14
women; mean age, 45.1 years) were free from
obvious underlying heart diseases (group RBBBN).
The remaining 24 patients with RBBB (19 men, five
women; mean age, 66.3 years) had the complication
of an old myocardial infarction (group RBBBML).
Of the 40 patients with LBBB, 22 (13 men, nine
women; mean age 61.2 years) were without gross
cardiovascular abnormalities (group LBBBN). The
other 18 patients with LBBB (11 men, seven women;
mean age, 70.4 years) had the complication of an
old myocardial infarction (group LBBBMI).
Diagnosis of myocardial infarction was presumed
by a history of prolonged chest pain accompanied
by typical electrocardiographic changes and elevation of creatine phosphokinase (CPK), and myocardial infarction was confirmed either by the transmural perfusion defect in `01T1 myocardial scintigraphy
or wall motion abnormalities (akinesis or dyskinesis) in left ventriculography. The age of the myocardial infarctions ranged from 6 months to 8 years
(mean, 4.3 years) in group RBBBMI, and it ranged
from 2.5 years to 11 years (mean, 6.1 years) in
group LBBBMI.
The locations of myocardial infarction determined by either left ventriculography or myocardial
scintigraphy were anterolateral (12 patients), inferior (seven patients), anterior and inferior (four
patients), and inferoposterior (one patient) in group
RBBBMI and were anterior (12 patients) and inferior
(six patients) in group LBBBMI.
Body surface maps were recorded by an
HPM65001415 (Chunichi Denshi, Japan) with 87
unipolar electrodes. IQRST maps (units, ,VV sec)
were made by minicomputer JEC980B (Nihon Denshi, Japan).
The PR segment on ECG was used as a baseline
to calculate the area under the curve. Time instants
of QRS onset and T offset were determined manually using lead V4 of the magnified ECG. The normal
mean IQRST map was derived from 50 normal individuals (44 men, six women; mean age, 38.3 years),
and each group's IQRST map was compared with the
normal mean lQRST map by a correlation coefficient
according to previous methods of Abildskov et al,16
Lux et al,'7 and Walker et al.'8 In addition, pattern
differences of IQRST maps from normal subjects and
patients were compared to assist in discrimination.
When the isointegral value in each lead point in
the IQRST map was less than the mean -2 SD, the
reduction was considered statistically significant.
The significant difference map of the IQRST map
(IQRST difference map) was based on the area of
significant reduction of IQRST values (significant area),
and the following parameters were derived from the
significant area to represent the size of the difference map: nDM, number of lead points in the
difference map; IDM, sum of the value obtained by
543
subtracting the normal mean IQRST value from the
IQRST value of a given patient at each point in the
difference map.
Statistical Analysis
The sensitivity [true-positive/(true-positive+falsenegative)], specificity [true-negative/(true-negative+
false-positive)], predictive value of a positive test
[true-positive/(true-positive + false-positive)], predictive value of a negative test [true-negative/
(true-negative+false-negative)], diagnostic accuracy
[(true-positive + true-negative)/total group] were
determined and expressed as a percentage.
Discriminant analysis was used to determine the
diagnostic criteria for detecting complicated myocardial infarction by the parameters, nDM and
.DM. Usual parametric, linear discriminant analysis was applied with nDM or SDM, which were the
explanatory variables, and myocardial infarction
complicated or uncomplicated, which were the discriminant items.
To increase the statistical validity, a procedure
was performed in which two samples were chosen at
random for each subgroup to calculate the jackknife
estimates. To compare the difference of the mean
values of nDM and EDM between groups, analysis
of variance (one-way layout) and multiple comparisons were performed, and the null hypothesis was
rejected when the p value was less than 0.05.
Results
IQRST Maps in Normal Subjects
In the normal mean IQRST map (Figure 1), the
positive area covered most of the chest with the
maximum located at V4 of the ECG and the minimum at the upper region of the sternum. The zero
line in the chest ran from the right lateral chest
toward the left shoulder, intersecting the V, area.
IQRST Map and IQRST Difference Map of Patients
With Right Bundle Branch Block
Group RBBBN. In group RBBBN patients, the
locations of the maximum and minimum of the lQRST
map were nearly the same as those locations for the
normal mean IQRST map, resulting in very similar
map patterns (Figure 2). The IORST difference map
was obtained in only seven of 40 patients (17.5%).
Group RBBBMI. In the IQRST map of RBBBMI
patients with anterolateral myocardial infarction
(Figure 3), the negative area was in the upper region
of the left chest and back, and the minimum was in
the upper region of V4. The positive area extended
to the right chest and to the lower area of the left
chest and back, and the maximum was at the lower
region of V,. Significant area appeared in the left
precordium, and V4 was at the center in IQRST
difference map.
In patients with inferoposterior myocardial infarction (Figure 4), the negative area in the IQRST map
was in the lower portion of the torso, and the
Circulation Vol 80, No 3, September 1989
544
Normal
Mean
IQRST
Map
FIGURE 1. Normal mean IQRST (QRST time
integral) map from 50 nornal subjects. The
rectangular frame represents the torso, of
which the left half represents the chest and
the right half the back. Thus, both the left
and right margins represent the rtight axillary
line. Six dots in the chest represent the positions of V1rV6 in standard 12-lead electrocardiogram. + and -, the maximum and minimum, respectively. Increments for the time
integral line are 10 ,uV* sec. Average magnitudes of the maximum and minimum were
136 ,uVsec and -39 gVsec, respectively.
3
Max. 136
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minimum was at the left lower chest. The positive
area occupied most of the upper region of the chest,
and the maximum was at the area above V2 and V3.
The significant area appeared widely in the lower
region of the torso in the IQRST difference map.
The significant area appeared in all patients in
group RBBBMI, and its area was closely related to
the location of infarction. The significant area
appeared in the middle and left lateral region of the
chest in patients with anterolateral infarction, in the
lower region of the chest and back in patients with
NAin. -39
inferior infarction, and in the middle of the left back
in patients with posterior infarction.
IQRST Map and IQRST Difference Map of Patients
With Left Bundle Branch Block
Group LBBBN. The distribution pattern of the
positive and negative areas of the IQRST map of
group LBBBN was quite similar to that of the
normal mean IQRST map. However, the negative
value was large in the middle and lower regions of
the right chest and back, resulting in the appearance
IQRST Map
IQRST Map
CRBBB without MI
'
K.Y. 78 M
283
CRBBB+Anterolateral MI
"
585C
IQRST Difference Map
Max. 33 Min. -21
IQRST Difference Map
a
~
~
~a.1~
~5
1
a
-5
9
a
aa
9
*~~~~~~
*
L
FIGURE 2. IQRST and IQRST (QRST time integral) difference maps of complete right bundle branch block (CRBBB)
without myocardial infarction (MI). No significantly
reduced area appeared in the IQRST difference map. Numbers under the IQRST map are maximal and minimal values
of the QRST time integral map.
a
a
a
.
2
aa
A
FIGURE 3. IQRST and IQRST (QRST time integral) difference maps in a patient with complete right bundle branch
block (CRBBB) complicated by anterolateral myocardial
infarction (MI). Stippled area in the IQRST difference map
is the significant area that was located in the left precordium. See text for details.
Hayashi et al Isointegral Maps
IQRST Map
CRBBB+Inferoposterior Ml
545
IQRST Map
F.l. 67 M
CLBBB without Ml
S.T. 73 M
IQRST Difference Map
IQRST Difference Map5
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
0*
*
a
a
a
a
a
a
a
IQRST and IQRST (QRST time integral) differofcomplete left bundle branch block (CLBBB)
without myocardial infarction (MI). Small significant
area emerged in the middle of the right lateral chest.
FIGURE 5.
FIGURE 4. IQRST and IQRST (QRST time integral) difference maps in a patient with complete tight bundle branch
block (CRBBB) complicated by inferoposterior myocardial infarction (MI). The significant area emerged in the
inferior torso.
of
a
significant
area
in the same region in the IQRST
difference map (Figure 5). The significant area was
found in the above region in the lQRST difference map
in 17 patients (77.3%).
Group LBBBMI. The negative area covered the
entire chest in the IQRST map in group LBBBmI
patients with anterior myocardial infarction (Figure
6). The minimum near V3 was remarkably smaller
than normal, and the maximum was displaced toward
the lower region of V6. The significant area covered
a wide region in the left chest, and the center was at
the V3-V5 area.
In patients with inferior infarction, the negative
area in the lQRST map extended to the inferior region
of the right chest and back (Figure 7). The significant
area was
in the inferior
area
of the torso.
The significant area was present in all patients in
the LBBBML group and was closely related to the
location of myocardial infarction. It appeared in the
middle of the left chest in patients with anterior
infarction and in the lower portion of the chest and
back in patients with inferior infarction.
Correlation Coefficient Between Normal Mean
IQRST Map and IQRST Map of Each Group
The correlation coefficient between the normal
mean lQRST map and the IQRST map in group RBBBN
was 0.85+±0.10 (mean±SD), and 13 patients in whom
the significant area appeared in the IQRST difference
ence maps
had a map correlation coefficient of less than
0.83 (Figure 8).
The correlation coefficient for group RBBBMI was
0.24±0.36, which was significantly lower than that
for group RBBBN (p<0.001). The correlation coefficient for group LBBBN was 0.71±0.14, which was
slightly lower than that for group RBBBN (NS). The
significant area appeared in the IQRST difference map
whenever the correlation coefficient was less than
0.84%.
The correlation coefficient for group LBBBMI was
0.03±0.34, which was significantly lower than that
for group LBBBN (p<0.001).
map
Diagnostic Ability of an Emergence of a
Significant Area in IQRST Difference Map to
Identify Myocardial Infarction Complicated by
Bundle Branch Block
In all patients, the significant area emerged in the
IQRST difference map when bundle branch block was
combined with myocardial infarction irrespective of
the site of block (Table 1).
The significant area emerged in fewer patients in
group RBBBN than in group LBBBN, resulting in
the higher specificity in the former (82.5% vs.
77.3%).
The negative predictive value was 100% in both
groups; however, the positive predictive value was
low, especially in group LBBB. The diagnostic
accuracy was 89.1% and 57.5% in groups RBBB
and LBBB, respectively.
546
Circulation Vol 80, No 3, September 1989
* P(D.001
IQRST Map
I mean±SD
L.-
H*
*
i
:
0.5-
1 1
IQRST Difference Map
a*
.1
.
.
.
.
.
W-
a
1f
I
0-
.
I
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
!
i~
1
-0.5Group RBBB. N
(40)
(N)
.
a
a
.
a
FIGURE 6. IQRST and IQRST (QRST time integral) differin a patient with complete left bundle branch
block (CLBBB) complicated by anterior myocardial infarction (MI). The significant area emerged in the wide area
in the left chest.
ence maps
IQRST Map
IQRST Difference Map
S
A
v
*
.
, *a
*
v
.
.
1
FIGURE 7. IQRSTandIQRST (QRST time integral) difference
in a patient with complete left bundle branch block
(CLBBB) complicated by inferior myocardial infarction
(MI). The significant area was located in the inferior torso.
maps
RBBB.MI
(24)
LBBB*N
(22)
LBBB-MI
(18)
FIGURE 8. Correlation coefficients between the normal
mean IQRST map and IQRST (QRST time integral) map of
each group.
Values for jackknife estimates were nearly equal
to those obtained by the routine statistical proce-
dures (Table 1).
Comparison of nDM and YDM of the IQRST
Difference Map in Each Group
Both nDM and SDM were larger in the groups
complicated by myocardial infarction (groups
RBBBMI and LBBBMI) than in groups without infarction (groups RBBBN and LBBBN) (Figure 9). Both
nDM and SDM were significantly larger in group
LBBBN than in group RBBBN.
Ability of nDM and 5DM of IQRST Difference Map
to Identify Myocardial Infarction Complicated by
Bundle Branch Block
Diagnostic ability for identifying complicated myocardial infarction with nDM and IDM values derived
from the discriminant analysis was tested. In group
TABLE 1. Diagnostic Accuracy of Emergence of a Significant Area
in IQRST Difference Map to Identify Myocardial Infarction Complicated by Bundle Branch Block
Group
Group
RBBB
LBBB
100 (100)
100 (100)
Sensitivity (%)
82.5 (82.5)
77.3 (77.3)
Specificity (%)
Predictive value (+) (%)
77.4 (77.7)
51.4 (51.5)
Predictive value (-) (%)
100 (100)
100 (100)
89.1 (89.1)
Diagnostic accuracy
57.5 (57.5)
Values in parentheses are the jackknife estimates.
RBBB, right bundle branch block; LBBB, left bundle branch
block.
Hayashi et al Isointegral Maps
nSub
|,uVsec
30
I-
2000
TT
mean±SE
20
1000
10
* P0.05
** P<O.01
*** P<0.001
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
Group
(N)
RBBB.N RBBB-MI LBBB.N LBBB-MI
(40)
(24)
(22)
(18)
FIGURE 9. Comparison of nDM and
diference map for each group.
useful for clinically diagnosing myocardial
infarction in various locations that are hard to
detect by ECG.16-27 Musso et a17 recently developed a procedure using body surface maps with a
preliminary learning set of maps to allow classification of LBBB with and without infarction. Whether
or not body surface mapping is useful for these
cases has not yet been sufficiently studied.
In recent years, ECG isointegral maps have been
clinically applied to diagnose various cardiac
diseases11,28-31 based on Wilson's concept of ventricular gradient13 verified through experimental
studies,11'32-34 theoretical consideration,35 and clinical observations.30
The present study was carried out to determine
the clinical usefulness of IQRST maps to correctly
diagnose myocardial infarction complicated by bundle branch block. IQRST maps of the normal mean
and of group RBBBN were similar to each other.
These were predominantly characterized by a
smooth bipolar body surface distribution pattern12
with a high correlation coefficient between these
two maps, which indicates that the ventricular
gradient was unaffected by the abnormal ventricular
activation sequence or the consistency of ventricular gradient.35 On the other hand, the IQRST map of
group LBBBN was slightly different from that of the
normal mean in the distribution of the negative
area, suggesting the possibility that the ventricular
gradient is somewhat affected by the ventricular
activation sequence. Left bundle branch block is
often associated with a variety of cardiac
abnormalities,36'37 especially in elderly patients such
as those in the present study. We cannot exclude
the possibility that group LBBBN included patients
with a cardiac disease that resulted in a IQRST map
pattern somewhat different from the normal mean.
The IQRST map pattern was quite different from the
normal mean map pattern in the presence of myocardial infarction, which was shown by a low correlation coefficient in the present study as Abildskov showed experimentally.38'39
* The area of significant reduction of integral values (i.e., significant area) in the lQRST difference map
ping is
ISub
4Or
WDM in IQRST
RBBB, the diagnostic accuracy was 98.4% by either
nDM'13 or YDM'816, and the discriminant probability was 87.9% and 93.9%, respectively (Table 2).
In group LBBB, the .diagnostic accuracy was
77.5% by nDM-'21 and 87.5% by IDM.1,350, and
the discriminant probability was 80.9% and 85.4%,
respectively. WDM.I816 and SDM.1,350 resulted
in greater diagnostic accuracy in detecting infarction complicated by right and left bundle branch
block, respectively.
Values for jackknife estimates were nearly equal
to those obtained by the routine statistical procedures (Table 2).
Discussion
General
It is not unusual to encounter patients with myocardial infarction complicating bundle branch block
that is difficult to diagnose correctly by ECG despite
many attempts at defining diagnostic criteria.2-6
Many reports have shown that body surface map-
547
TABLE 2. Ability of nDM and EDM to Identify Myocardial Infarction Complicated by Bundle Branch Block
Group RBBB
Group LBBB
IDM'816
DNDM. 1,350
nDM' 13
nDM'21
77.8 (77.8)
77.8 (77.8)
95.8 (95.8)
95.8 (95.8)
Sensitivity (%)
95.5 (95.5)
100 (100)
100 (100)
77.3 (77.3)
Specificity (%)
93.3 (93.8)
73.7 (74.2)
100 (100)
100 (100)
Predictive Value (+) (%)
84.0 (84.3)
81.0 (81.2)
97.6 (97.6)
97.6 (97.6)
Predictive Value (-) (%)
87.5 (87.5)
77.5 (77.5)
98.4 (98.4)
98.4 (98.4)
Diagnostic Accuracy (%)
87.9*
80.9t
85.4§
Discriminant
93.9t
Probability (%)
Values in parentheses are jackknife estimates.
RBBB, right bundle branch block; LBBB, left bundle branch block.
Discriminant function: *Z=2.978-0.225 nDM; tZ=5.114-0.00627 ;DM; tZ=3.390-0.164 nDM; §Z=3.9230.0029 IDM.
548
Circulation Vol 80, No 3, September 1989
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suggested the location of infarction in patients with
complicated myocardial infarction as Flowers et
al20'21'40 reported.
When diagnostic ability of a significant area in the
IQRST difference map was examined to identify infarction, sensitivity and negative predictive value was
100% in groups RBBB and LBBB. Diagnostic accuracy was satisfactory in group RBBB only by using
the parameter of presence or absence of a significant area, but accuracy was not high enough for
clinical use in group LBBB.
Because a significant area appeared in the IQRST
difference map in some patients in groups RBBBN
and LBBBN, we examined whether or not the
determination of the critical size of a significant area
obtained by the discriminant analysis would improve
diagnostic power. In group RBBB, diagnostic accuracy was 98.4% by nDM _ 13 and by IDM.'816,
which showed a much higher diagnostic accuracy
than by the emergence of a significant area only.
The discriminant probability obtained when using
these parameters was high enough for a clinical use.
Diagnostic accuracy of nDM'21 and SDM'1,350
in group LBBB was also improved compared with
the diagnostic accuracy by the emergence of a
significant area only, and it was high enough for a
clinical use.
Because LBBB is frequently complicated by a
variety of cardiac pathologic changes36,37 that are
clinically obscure, values of nDM and YDM for the
diagnostic criteria in group LBBB to detect coexisting myocardial infarction were larger than those
in group RBBB. Parameters nDM and IDM proved
to be very useful for detecting infarction in groups
RBBB and LBBB, and the emergence of a significant area only was also practically useful in diagnosing an infarction in group RBBB because of its
simplicity as a parameter.
The present study showed that by using IQRST
maps and the variables derived from the maps
(nDM and SDM), patients with myocardial infarction complicated by bundle branch block could also
be diagnosed satisfactorily, although they could not
be diagnosed by the QRS isointegral map.41'42
Limitations
The diverse conditions associated with LBBB
suggest that a nonspecific pathologic process may
also be common to most etiologic factors. Patients
in group LBBBN were quite elderly, and pathologic
process due primarily to aging in these patients may
mimic myocardial infarction, resulting in the appearance of significant areas in the lQRST difference map.
In addition, the alteration of depolarization sequence
may be greater in left bundle branch block than in
right bundle branch block, and this may have a
greater influence on the ventricular gradient.43"44
The age of myocardial infarction and bundle
branch block was variable in the present study
groups, and this could influence the result because
it has been shown experimentally to affect ventricular repolarization properties.43
Because lQRST difference maps depend greatly on
the normal mean IQRST map, the appropriate selection of normal subjects to make the latter map is
important. Standard maps derived from a large
number of normal subjects of different age groups,
sex, and body structure45 will be needed also for a
more reasonable comparison to patient populations.
The correlation coefficient is independent of the
potential magnitudes of the two maps and only
gives an indication of the similarities in potential
distributions. More precise study regarding the similarities of absolute values of maps including surface
potentials may be required.
The values of nDM and IDM derived from the
present retrospective study need to be tested in a
prospective study on a larger scale to confirm their
validity in screening or diagnostic tests. As an
alternative method, a jackknife procedure was used
to increase the statistical validity of this study with
a limited number of patients. The values for the
jackknife estimate were almost equal to those
obtained by routine statistical procedures, and statistical values shown in Tables 1 and 2 were considered to be reasonable.
Clinical Implications
When the ventricular gradient is used to detect
myocardial infarction complicated by conduction
disturbances, sensitivity and specificity are often
unreliable because the normal range for ventricular
gradient is wide46 and because diagnosis of the
location of myocardial infarction is difficult by this
parameter. There are also occasional false-negative
findings by this method.47
The lQRST difference map has advantages in detecting myocardial infarctions complicated by bundle
branch block through its ability to detect the primary differences between normal and abnormal
repolarization properties. This suggests that diagnosis of these cases could be more accurately performed if the diagnostic criteria are further refined
through the prospective study on a larger scale by
using a sex-matched normal control group.
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KEY WORDS * ST-T changes * body surface mapping X
QRST time integral map * myocardial infarction
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
Diagnostic value of QRST isointegral maps in detecting myocardial infarction
complicated by bundle branch block.
H Hayashi, S Watabe, S Yabe, K Takami, S Ohsugi, M Hirai, M Mizutani and H Saito
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2016
Circulation. 1989;80:542-550
doi: 10.1161/01.CIR.80.3.542
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