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533
Recovery-Phase Patterns of ST Segment
Depression in the Heart Rate Domain
Identification of Coronary Artery Disease by the
Rate-Recovery Loop
Peter M. Okin, MD, Olivier Ameisen, MD, and Paul Kligfield, MD
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Although the time course of ST segment depression after exercise has been related to the
presence and severity of coronary artery disease, recovery-phase patterns of ST segment
depression with reference to changing heart rate have not been quantified. We have found
distinct recovery loop patterns of ST segment depression that distinguish subjects without
coronary disease from patients with coronary artery disease when ST segment depression is
examined in the heart rate domain. Continuous plots of ST segment depression and heart rate
were constructed throughout treadmill exercise and recovery in 100 clinically normal subjects,
in 124 patients with coronary artery disease proven by catheterization, and in 17 patients with
no significant coronary disease at catheterization. Among clinically normal subjects, 95% (95 of
100) had normal (clockwise) rate-recovery loops, and 5% (five of 100) had abnormal
(counterclockwise) rate-recovery loops. In these normal subjects, the resulting 95% specificity
of a normal rate-recovery loop was similar to the 93% (93 of 100) specificity of standard
end-exercise ST segment depression criteria. Among patients with coronary disease proven by
angiography, 93% (115 of 124) had abnormal (counterclockwise) rate-recovery loops, and 7%
(nine of 124) had normal rate-recovery loops. In contrast was the significantly lower 74% (92
of 124) sensitivity of standard ST segment criteria (p<0.001 vs. the rate-recovery loop).
Specificity of a normal rate-recovery loop (71%, 12 of 17) and standard ST segment depression
criteria (71%, 12 of 17) were similar in the patients with normal coronary arteries at
angiography. We conclude that the pattern of ST segment depression as a function of heart rate
during exercise and recovery can markedly enhance the accuracy of the exercise electrocardiogram for the identification of coronary artery disease. (Circulation 1989;80:533-541)
E a xercise electrocardiography remains the most
widely used method for assessing the presence and severity of coronary artery
disease.'-4 Because of the poor sensitivity of standard ST segment depression criteria at end exercise
alone for the identification of coronary disease,5,6
additional diagnostic information has been sought
from the time course and magnitude of ST segment
depression during the postexercise recovery
phase.2,7-14 Simple evaluations of the duration of
ischemic ST segment responses into recovery,8-12
as well as complex algorithms that depend on the
magnitude, slope, and duration of ST segment
depression throughout exercise and recovery,2,7,13'14
have been reported to enhance test accuracy.
From the Division of Cardiology, Department of Medicine,
The New York Hospital-Cornell Medical Center, New York,
New York.
Address for correspondence: Dr. Okin, Division of Cardiology, Department of Medicine, The New York Hospital-Cornell
Medical Center, 525 East 68th Street, New York, NY 10021.
Received January 26, 1989; revision accepted May 2, 1989.
Recent work has also shown the ability of heart
rate-adjusted indexes of ST segment depression during exercise to improve the accuracy of the exercise
electrocardiogram for identifying coronary disease
and assessing its severity.'5-23 Although patterns
relating ST segment depression to heart rate during
exercise and recovery were described in early reports
from Bruce and colleagues,24-28 the potential diagnostic value of heart rate-dependent behavior of ST
segment depression during recovery has not been
quantified.29 Based on these observations, we examined whether or not distinct recovery-phase patterns
of ST segment depression, in relation to heart rate
rather than time, could separate patients with and
without coronary disease more accurately than standard end-exercise criteria or time-dependent ST segment changes during recovery.
Methods
Study Population
The records of 241 patients who underwent exercise electrocardiography at The New York Hospital-
534
Circulation Vol 80, No 3, September 1989
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Cornell Medical Center were reviewed. Clinical
data and exercise-phase electrocardiographic findings of a smaller subset of these patients have
previously been reported in detail.21,23
The first group (clinically normal) consisted of
100 consecutive, asymptomatic, unmedicated subjects referred by their physicians for exercise electrocardiography as part of a comprehensive screening evaluation or as a precautionary evaluation
before beginning an exercise program.23 There were
81 men and 19 women whose mean age was 47±+13
(SD) years. Each had normal findings on cardiac
examination and resting electrocardiogram before
exercise; no subject was included in this group if
exercise systolic blood pressure exceeded 210
mm Hg or if exercise was limited by chest pain.
The second group (stable angina) consisted of 141
consecutive patients with effort-related chest pain
referred to The New York Hospital-Cornell Medical Center for diagnostic coronary arteriography,
who underwent exercise testing at the time of
hospital admission as part of a prospective evaluation of the ST segment/heart rate slope for the
identification of anatomically extensive coronary
obstruction.21 Patients with coexisting valvular heart
disease, left bundle branch block on the resting
electrocardiogram, myocardial infarction within 8
weeks of arteriography, or unstable angina were
excluded from this group. There were 111 men and
30 women in this group whose mean age was 57±9
years; 124 had coronary disease, and 17 had no
significant coronary disease (by 50% luminal obstruction criteria). In this group, 28% (40 6f 141) had a
history of remote myocardial infarction, and 16%
(23 of 141) had electrocardiographic evidence of a
previous Q wave myocardial infarction. There were
23 patients in this group who were not receiving
medications; among the remaining 118 patients, 92
were taking /3-blocking drugs, 79 were taking
nitrates, 76 were taking calcium channel blocking
drugs, and only five were taking a digitalis preparation at the time of exercise evaluation.
Exercise Electrocardiography
Exercise electrocardiograms were performed on
a treadmill with a Computer Assisted System for
Exercise (CASE II) (Marquette Electronics, Milwaukee, Wisconsin), modified by the addition of a
bipolar CM5 lead to the standard 12-lead recording
system. All patients exercised according to the
Cornell protocol, our more gently graded modification of the Bruce protocol that produces small heart
increments between stages, with alternate stages of
the Cornell protocol directly comparable with standard Bruce protocol workloads.30 Age-adjusted target heart rates were sought as the exercise endpoint
for all studies, but tests were terminated when
necessary because of limiting chest pain, dyspnea,
or fatigue. As is customary in our laboratory, all
patients walked at 1.7 mph at 0% grade for the first
3 minutes of recovery and remained upright through-
out the remainder of the
period.
postexercise recovery
Exercise tests were evaluated with standard electrocardiographic criteria measured from the raw
intraexercise tracings in each study.9 The test was
considered positive in the presence of either 0.1 mV
or more of additional downsloping or horizontal ST
segment depression, or 0.15 mV or more of additional upsloping ST segment depression, measured
between 60 and 80 msec after the J point, at the end
of exercise.
ST Segment Depression in Relation to
Heart Rate and Time
In addition to standard electrocardiographic output during exercise, the CASE II provides continuously updated, computer-based measurement of
ST segment levels in each lead, based on incremental averaging of normal complexes during exercise.
Computer-calculated ST segment amplitudes (both
depression and elevation), measured to the nearest
10 ,uV at a point 60 msec after the J point with the
end of the PR segment as a reference, were obtained
in each lead after each stage of exercise, at peak
effort, and after each minute of recovery. Accuracy
of this measurement has been previously validated
in our laboratory.30
The recovery-phase patterns of ST segment
depression with reference to changing heart rate
were examined by constructing continuous plots of
absolute ST segment deviation and heart rate
throughout treadmill exercise and recovery, with
both ST elevation and depression values used for
analysis. Analysis was performed in the lead with
the most ST segment depression at end exercise,
but leads aVR, aVL, and V1 were ignored. When no
ST segment depression was present, the lead with
the least amount of ST segment elevation at end
exercise was selected for analysis. ST segment
depression was plotted in the upward direction, and
ST segment elevation was plotted in the downward
direction (Figure 1).
The behavior of ST segment depression during
recovery with reference to time was evaluated by
constructing similar plots of ST segment deviation
as a function of the time (in minutes) before and
after peak exercise (Figure 2). The time-dependent
behavior of ST segment depression in recovery was
further analyzed for the presence of persistent ST
segment depression 0.1 mV or more at 1 minute into
recovery.8-10
Definition of Recovery-Phase Patterns of ST
Segment Depression
Preliminary observations revealed that clinically
normal subjects with ST segment depression at end
exercise often exhibited a distinct pattern of
recovery-phase ST segment depression as a function of heart rate (Figure 1). Because ST segment
depression was lower at early recovery-phase heart
rates than at corresponding exercise heart rates,
Okin et al Recovery Phase ST Segment Depression
CLOCKWISE
RATE-RECOVERY LOOP
COUNTERCLOCKWISE
RATE-RECOVERY LOOP
-150
ST DEPRESSION
Ji
-100
-50_
ST SEGMENT
LEVEL
0
(AV)
50k
If Exercise
1° Recovery
100
Clinical normal
133-43-74
ST ELEVATION
80 100 120 140
HEART RATE (bpm)
60
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80 100 120 140
HEART RATE (bpm)
there was a clockwise loop of ST segment depression as a function of the heart rate during exercise
and recovery. This pattern was defined as a normal
rate-recovery loop.
In contrast, patients with coronary artery disease
often exhibited the opposite pattern of ST segment
depression in relation to heart rate: ST segment
depression was greater at recovery-phase heart
rates than at corresponding exercise heart rates,
producing a counterclockwise loop of ST segment
depression as a function of the heart rate during
exercise and recovery. This pattern was defined as
an abnormal rate-recovery loop (Figure 1).
As a function of time, rather than heart rate, the
recovery-phase pattern of ST segment depression in
clinically normal subjects was also generally in a
clockwise pattern (Figure 2). This pattern was
defined as a normal time-recovery loop. As will be
shown, no distinct behavior of ST depression in the
time domain emerged for patients with coronary
CLOCKWISE
TIME-RECOVERY LOOP
-150
7
ST DEPRESSION
I,
-100
-50
ST SEGMENT
LEVEL
-
I
Coronary Angiography
Selective coronary cineangiography was performed by means of the Judkins technique in all
stable angina patients. Multiple views were obtained
in all patients, with the left anterior descending and
left circumflex coronary arteries visualized in at
least four views and the right coronary artery in at
least two views. The results were interpreted separately from the original report, specifically for the
purpose of our exercise test studies, by a single
experienced angiographer using calipers, without
knowledge of clinical or exercise test data as previously reported in detail.21'23
CLOCKWISE
TIME-RECOVERY LOOP
-100F
'.
I
\1 .64
0
o
(MV)
50
501
| Exercise
t
Recovery
100l
100
Clinical normal
132-43-74
ST ELEVATION
6
4
TIME (min)
2
0
FIGURE 1. Plots of STsegment deviation plotted as a function of heart
rate during exercise and recovery,
with STsegment depression shown in
the upward direction and STsegment
elevation shown in the downward
direction. Typical rate-recovery loops
are shownfor a clinically normal subject (left panel) andfor a patient with
coronary artery disease (right panel).
Despite similar heart rates and magnitude of ST segment depression at
peak exercise, the clinically nornal
subject had a clockwise pattem of ST
segment depression relative to heart
rate during recovery, whereas the
patient with coronary disease has the
opposite, counterclockwise pattern of
recovery. 2v-CAD, two-vessel coronary artery disease.
disease. Patients with coronary disease exhibited
both clockwise and counterclockwise loops of ST
segment depression as a function of the time in
exercise and recovery (Figure 2). For comparison
with findings in the heart rate domain, counterclockwise time-recovery loops were defined as abnormal.
-50k
I
'
-150r
535
2v-CAD
202-50-08
6
4
2
TIME (min)
0
FIGURE 2. Plots of ST segment
deviation plotted as a function of
time before and after peak exercise
in the same clinically normal subject
(left panel) and patient with coronary artery disease (right panel) in
Figure 1. Although the clinically normal subject had clockwise behavior
of recovery-phase ST segment
depression in relation to time, the
patient with coronary disease also
showed a similar clockwise timerecovery loop. 2v-CAD, two-vessel
coronary artery disease.
536
Circulation Vol 80, No 3, September 1989
TABLE 1. Group Characteristics and Exercise Performance
Clinically
normal
Characteristic
(n = 100)
p
Age (yr)
47+12
<0.001
Sex (male/female)
NS
81/19
<0.001
18+3
Exercise duration
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(min)
93+7
<0.001
Proportion of target
rate achieved (%)
164±16
<0.001
Maximum heart rate
(beats/min)
<0.001
177±21
Maximum systolic
pressure (mm Hg)
29+5
<0.001
Maximum double
product (xlO 3)
(mm Hgx [beats/mini)
Data are mean±SD.
CAD, coronary artery disease.
*Clinically normal subjects vs. CAD by catheterization;
catheterization vs. clinically normal subjects.
CAD by
catheterization
(n = 124)
58+9
103/21
9+4
pt
NS
<0.05
NS
No CAD by
catheterization
(n = 17)
54+10
9/8
11+4
pt
<0.05
<0.05
<0.001
66+10
<0.001
76+ 15
<0.001
112±18
<0.001
132+28
<0.001
157±22
NS
161+19
<0.05
18±4
<0.05
21+6
<0.001
tCAD by catheterization
Degree of stenosis was defined as the greatest
percent reduction of luminal diameter in any view
compared with the nearest normal segment. For
classification of the number of obstructed coronary
arteries, disease was considered significant when
50% luminal obstruction was present. Left main
narrowing of 50% or greater was scored as the
equivalent of two-vessel disease.1718,21,23 According
to these criteria, there were 17 patients with no
significant disease, 34 with one-vessel disease, 43
with two-vessel disease, and 47 with three-vessel
coronary disease. Ten patients had left main coronary disease, including four with additional twovessel disease and six with additional three-vessel
disease. Of note, 96% (119 of 124) of the patients
with coronary disease defined by 50% stenosis also
had at least 75% luminal obstruction of one or more
major vessels.
Data Analysis
Sensitivity and specificity were calculated accord-
ing to standard definitions.31 Test specificity was
tested separately in the 100 clinical normal subjects
and in the 17 patients with no significant coronary
disease at angiography. Test sensitivity was assessed
in the 124 patients with angiographically proven
coronary disease. Comparison of test performance
of standard exercise test criteria and the timerecovery loop with outcome based on the raterecovery loop was performed in each group by
McNemar's modification of the x2 method for paired
proportions. In addition, sensitivity of each method
was compared for patients with demonstrated coronary disease subgrouped by the number of
obstructed coronary arteries. Sensitivity of the raterecovery loop was further assessed with patients
subgrouped by medication usage and by a history of
or electrocardiographic evidence of previous myocardial infarction.
vs. no CAD
by catheterization; tno CAD by
Statistical Analysis
Mean values for all findings are reported with the
standard deviation (SD) as the index of dispersion.
Comparison of mean values among groups was
performed by one-way analysis of variance, with
post hoc testing of individual group differences by
Scheffe's method. Comparison of subgroup proportions was performed by x2 analysis with correction
for continuity. For tests of proportion and for post
hoc testing of mean values, ap value less than 0.05
was required for rejection of the null hypothesis.
Results
Group Characteristics and Exercise Perfornance
Group characteristics and exercise performance
are shown in Table 1. Patients with coronary disease were similar to clinically normal subjects with
respect to sex distribution, but there was a higher
proportion of women among the catheterized
patients with no significant coronary obstruction.
Maximum predicted heart rate achieved, peak exercise heart rate, and maximum double product were
higher in clinically normal subjects than in the
patients without coronary disease, and these were
higher in patients with no demonstrated disease at
angiography than in those with coronary disease.
Patients with coronary disease were older and exercised for a shorter period of time and to lower peak
systolic pressures than clinically normal subjects,
but they were similar to stable angina patients
shown to have no coronary disease by these findings.
Test Performance of the Rate-Recovery Loop
Test performance for the rate-recovery loop is
compared with performance of standard test criteria
and time-dependent recovery-phase criteria in Table
2. Among clinically normal subjects, 95% (95 of
Okin et al Recovery Phase ST Segment Depression
537
TABLE 2. Sensitivity and Specificity of the Rate-Recovery Loop, Time-Recovery Loop, and Standard ST Segment Criteria
Sensitivity
CAD by
catheterization
(n = 124)
93% (115/124)
74% (92/124)t
35% (44/124)t
51% (63/124)t
Specificity
Clinically
normal
(n = 100)
95% (95/100)
93% (93/100)
96% (96/100)
99% (99/100)
Criteria*
Rate-recovery loop
Standard ST segment
Time-recovery loop
ST depression at
1 min recovery
CAD, coronary artery disease.
*See text for definitions of test criteria.
tp<0.001 vs. rate-recovery loop.
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100) had normal (clockwise) rate-recovery loops,
and 5% (five of 100) had abnormal (counterclockwise) rate-recovery loops. Of the 95 subjects with
clockwise rate-recovery loops, 51 had end exercise
ST segment depression ranging from 10 to 180 gV,
and 44 had no ST segment depression in any lead at
end exercise. Despite the absence of end exercise
ST segment depression, all 44 of these subjects had
a clockwise pattern of absolute ST segment deviation when changing amounts of ST segment elevation were examined as a function of heart rate
during exercise and recovery.
In these normal subjects, the resulting 95% specificity of a normal rate-recovery loop was similar to
the 93% specificity of standard test criteria, the 96%
specificity of a normal (clockwise) time-recovery
loop, and the 99% specificity of ST depression
persisting at least 1 minute into recovery. Specificity of the rate-recovery loop was 71% (12 of 17) in
patients with stable angina who had normal coronary arteries at angiography; specificity was similarly low in this subgroup for both standard and
time-dependent recovery criteria (Table 2).
In patients with angiographically proven coronary disease, 93% (115 of 124) had abnormal (counterclockwise) rate-recovery loops (Table 2), and all
nine patients with false-negative rate-recovery loops
had clockwise loops. In contrast was the significantly lower 74% sensitivity of standard test crite-
No CAD by
catheterization
(n = 17)
71% (12/17)
71% (12/17)
82% (14/17)
76% (13/17)
ria, 35% sensitivity of an abnormal (counterclockwise) time-recovery loop, and 51% sensitivity of an
abnormal test persisting at least 1 minute into
recovery (allp<0.001 vs. the rate-recovery loop).
Test Sensitivity in Relation to Extent of Coronary
Artery Disease
Test sensitivities of the rate-recovery loop pattern, standard test criteria, the time-recovery loop
pattern, and abnormal ST depression persisting at
least 1 minute into recovery are shown in relation to
anatomic extent of coronary disease in Table 3. Of
note, the rate-recovery loop identified 98% of
patients with three-vessel disease, and 93% (84 of
90) of patients with multivessel disease. In contrast,
standard test criteria identified only 83% of patients
with three-vessel disease and only 82% (74 of 90) of
patients with multivessel disease (p <0.05 vs. raterecovery loop). For each test, there was a trend
toward increased sensitivity with increasing numbers of obstructed arteries. However, this trend
was only modest for the rate- and time-recovery
loop criteria. Within each subgroup defined by
extent of obstruction, detection of coronary disease
by the rate-recovery loop was significantly greater
than by the other test criteria, except for similar
sensitivity of standard test criteria in patients with
two-vessel disease.
TABLE 3. Sensitivity of the Rate-Recovery Loop, Time-Recovery Loop, and Standard ST Segment Criteria According
to the Extent of Coronary Disease
One vessel
Criteria*
91% (31/34)
Rate-recovery
loop
53% (18/34)t
Standard ST
segment
35% (12/34)§
Time-recovery
loop
ST depression
24% (8/34)§
at 1 min
recovery
CAD, coronary artery disease.
*See text for definitions of test criteria.
Extent of CAD
Three vessel
Two vessel
88% (38/43)
98% (46/47)
Total CAD
93% (115/124)
81% (35/43)
83% (39/47)t
74% (92/124)§
30% (13/43)§
40% (19/47)§
35% (44/124)§
58% (24/43)t
64% (30/47)§
51% (63/124)§
tp<0.05 vs. rate-recovery loop; tp<0.01 vs. rate-recovery loop; §p<0.001 vs. rate-recovery loop.
538
Circulation Vol 80, No 3, September 1989
TABLE 4. Effect of Medications on Sensitivity of the RateRecovery Loop for Coronary Disease
Medication
Medication
/3-Blockers
Nitrates
Calcium blockers
present
95% (84/88)
93% (69/74)
94% (66/70)
Medication
absent
86% (31/36)
92% (46/50)
91% (49/54)
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Effect of Medications and Previous Infarction on
Sensitivity of the Rate-Recovery Loop
Test sensitivity of the rate-recovery loop in relation to medications used, presence of a Q wave
infarction on the resting electrocardiogram, and
history of a remote myocardial infarction are shown
in Tables 4 and 5. There was no significant difference in the ability of the rate-recovery loop to
identify coronary disease among patients who were
taking or were not taking ,3-blockers, long-acting
nitrates, or calcium channel blockers. Neither electrocardiographic evidence of previous Q wave myocardial infarction nor a history of infarction had a
significant effect on the sensitivity of the raterecovery loop, whereas there was a trend toward
lower test sensitivity of standard ST segment criteria among patients with a previous infarction. Of
note, among patients with coronary disease and
negative standard exercise tests, the rate-recovery
loop identified 92% (12 of 13) of patients with a
history of a myocardial infarction and 100% (seven
of seven) of patients with a previous Q wave
infarction.
Discussion
Early observations by Bruce and colleagues24-29
suggest that different heart rate-related postexercise
patterns of ST segment depression may occur in
individuals with and without coronary disease. Our
present data provide quantitative evidence of
improved diagnostic performance of these patterns
for identifying coronary artery disease.
TABLE 5. Effect of Previous Myocardial Infarction on Sensitivity
of the Rate-Recovery Loop and Standard ST Segment Criteria for
Coronary Disease
Electrocardiographic
Q wave infarction
Present (n=22)
Absent (n 102)
History of remote infarction
Present (n=39)
Absent (n=85)
*p<0.05
loop.
Rate-recovery
loop
Standard ST
criteria
95% (21/22)
92% (94/102)
68% (15/22)
75% (77/102)t
90% (35/39)
67% (26/39)*
94% (80/85)
78% (66/85)t
vs. rate-recovery loop; tp<0.01 vs. rate-recovery
Recovery-Phase Behavior of ST Segment
Depression in the Heart Rate Domain
Physiologic correlates of rate-recovery loop patterns can be found in previous observations that
compare myocardial ischemia during exercise and
recovery. Detry and colleagues28 found a close
linear relation of ST segment depression during
exercise to myocardial oxygen demand, as reflected
by tension-time index, in patients with coronary
disease. During recovery, however, this relation
was nonlinear, with similar ST segment depressions
observed at lower tension-time indexes than during
exercise. Also, exercise- or pacing-induced subendocardial ischemia has been well recognized to
continue into the recovery phase as shown by
persistent ST segment depression associated with
continued abnormal lactate production,32,33 regional
wall motion abnormalities,34 and diminished subendocardial blood flow to the affected area.35,36
Although these electrocardiographic, metabolic, performance, and perfusion abnormalities may be less
severe during early recovery than at peak pacing or
exercise,32-36 they remain greater relative to heart
rate during early recovery than during the development of ischemia.32,33,36
Although the magnitude of ST segment depression during exercise can be directly related to the
level of myocardial workload (as reflected by heart
rate) in patients with myocardial ischemia, ST segment depression during early recovery remains
greater than expected for the rapidly decreasing
myocardial oxygen demand that results from an
abrupt lowering of exercise load. In effect, relative
to heart rate, recovery-phase resolution of ST segment depression lags behind its exercise-phase development when coronary disease is present. This
results in the counterclockwise pattern of ST segment depression in the heart rate domain found in
our patients with coronary obstruction. In contrast,
rate-related resolution of repolarization change
exceeds its exercise phase development in normal
subjects, resulting in a clockwise pattern despite ST
segment depression at peak effort.
Because the rate-recovery loop is based on ST
segment changes surrounding peak effort, the direction of rotation is independent of the absolute
magnitude of ST depression at end exercise. Therefore, in most cases, the recovery-phase pattern
cannot be reliably predicted from exercise-phase
data alone. Over half of our normal subjects with
clockwise loops had measurable ST depression at
the end of exercise that was often similar in magnitude to that found at the onset of the counterclockwise loop pattern in patients with coronary disease.
However, all subjects with absolutely no ST depression in any lead at end exercise had clockwise
recovery-phase loop patterns when examined in the
context of changing amounts of ST segment elevation 60 msec after the J point. Whether or not
complete absence of ST depression at end exercise
Okin et al Recovery Phase ST Segment Depression
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alone might simply be interpreted as a normal test
response remains to be established, but a normal
pattern may occur even in cases with later recovery
phase ST depression if early recovery-phase behavior in these subjects initiates a clockwise pattern of
rotation.
Also of note, counterclockwise rate-recovery
loops in patients with coronary disease are not
simply markers for an increase in ST segment
depression during recovery as has been reported in
some patients with negative end exercise tests by
standard criteria.9,37 An increase in absolute magnitude of ST depression during recovery was seen in
only nine of our 124 patients with coronary disease,
including one patient who had ST segment depression that exceeded 0.1 mV only during recovery. In
these cases, early recovery-phase augmentation of
ST depression during heart rate slowing is an obvious indication of counterclockwise rotation. On the
other hand, ST depression was less during recovery
in the large majority of patients with coronary
disease, which was similar to the recovery-phase
behavior of ST depression in normal subjects, and
distinct rotation only became apparent by construction of the rate-recovery loop.
Recovery-Phase Behavior of ST Segment
Depression in the Time Domain
Unlike the patterns that result from reference to
heart rate, distinct recovery-phase behavior of ST
segment depression was not found in the time
domain. Nearly two thirds of patients with coronary
disease had clockwise time-recovery loops that
were indistinguishable from the time-recovery loops
of most normal subjects. The diagnostic value of
recovery loops in the rate domain, but not in the
time domain, highlights differences between heart
rate and time as estimates of myocardial work in the
period surrounding peak exercise. Heart rates at
matched times before and after peak exercise are
different. If the rate-recovery loop examines ST
segment depression during recovery and exercise at
approximately matched workloads, as reflected by
similar heart rates, it follows that the time-recovery
loop relates ST segment depression during exercise
and recovery at varying levels of myocardial oxygen demand. Our findings therefore indicate that the
time course of ST depression may be an indirect
and potentially inaccurate method for evaluating
myocardial ischemia.
Although the time-dependent pattern of ST segment depression during recovery was not a sensitive criterion for coronary disease in the present
study, other methods that incorporate the pattern of
ST segment changes as a function of time during the
postexercise period have been shown to improve
the ability of the exercise electrocardiogram to
identify coronary artery disease.2,7'13,14 Whether or
not accuracy of these methods might be further
enhanced by correction for rate, rather than time,
throughout exercise remains to be examined.
539
Improved Identification of Coronary Disease
The sensitivity of the rate-recovery loop for coronary disease is similar in magnitude to the improved
accuracy of other methods based on heart rate
correction of ST segment depression during exercise only.15-23 However, these new methods are
different in principle and may provide different
types of information. The nonlinear and complex
behavior of ST segment depression with respect to
heart rate during recovery28 indicates that this relation may be more difficult to quantify than the linear
rate-related changes in ST segment depression that
occur during exercise in patients with coronary
disease.15-23 Thus, although the ST segment/heart
rate slope is a continuous variable that can be
related to the anatomic and functional severity of
coronary obstruction,15-19,21-23 translation of
recovery-phase data to a complementary continuous variable may prove difficult.
Or the findings support the idea that the raterecovery loop provides diagnostic information distinct from ST segment criteria based on exercisephase findings. Sensitivity of the rate-recovery loop
appears to be relatively independent of the extent of
coronary artery disease (Table 3), unlike the performance of standard ST segment criteria2,9,10 and
heart rate-adjusted ST segment criteria that are
derived from exercise-phase data alone.15,23 The
strong dependence of the test sensitivity of other
electrocardiographic methods on the anatomic extent
of coronary disease results from threshold criteria
that are directly related to the severity of ischemia
induced by exercise.2,9,10,23 In contrast, the direction of the rate-recovery loop is not dependent on
any threshold magnitude of ST segment depression
at peak exercise; it may thus be less affected by the
anatomic and functional severity of underlying coronary artery obstruction than are standard test
criteria.
Similar reasoning may explain the absence of an
effect of cardiac medications or previous myocardial infarction on sensitivity of the rate-recovery
loop. /3-Blockers, by blunting the heart rate response
to exercise, have been found to reduce the magnitude of ST segment depression at peak exercise38,39
but do not markedly affect the rate-dependent pattern of ST segment depression during recovery.
Previous myocardial infarction may also result in a
diminished magnitude of ST segment depression
with exercise, leading to reduced sensitivity of
partition-based standard electrocardiographic
criteria.40,41 Remote myocardial infarction does not
adversely affect sensitivity of the rate-recovery
loop in the present population, but test performance
may vary in patients with recent infarction who
were excluded from this study.42
Limitations and Clinical Implications
Although the present data show that the raterecovery loop is highly sensitive for detecting cor-
540
Circulation Vol 80, No 3, September 1989
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onary artery disease in patients with stable angina,
these findings should not be extrapolated to other
populations without caution. Test sensitivity may
be lower in asymptomatic subjects with coronary
disease, and overall test performance may vary in
patients with other chest pain syndromes, such as
atypical angina. Test specificity may be lower in
patients with other causes of nonischemic ST segment depression than in our clinically normal
subjects.23,43X44 These important possibilities require
careful evaluation. Further, it must be appreciated
that predictive value of a positive rate-recovery
loop, like all imperfect diagnostic tests, will vary
with the population prevalence of disease.44,45 However, even with potential limitations, the raterecovery loop appears to represent a useful and
easily performed method for improving the diagnostic value of the exercise electrocardiogram.
Although our data show that the counterclockwise rate-recovery loop is a sensitive marker for
coronary artery disease, the relation of these findings to prognostically important myocardial ischemia remains to be clarified. Because we did not
measure myocardial ischemia per se, the mechanisms governing the direction of rate-recovery loops
in our patients with angina32-36 can only be speculated. Further evaluation is required to examine
whether or not the rate-recovery loop can separate
myocardial ischemia in patients with coronary disease from abnormal repolarization during exercise
in patients with noncoronary heart disease. Expansion of the loop method from a simple vector
analysis to a more complex continuous variable that
incorporates a magnitude term would be required
for comparison with independent measures of the
extent of exercise-induced myocardial ischemia.
Thus, at present, the rate-recovery loop may best
serve as a simple screen for the presence or absence
of underlying coronary obstruction. Additional quantitative exercise-phase findings, such as the ST
segment/heart rate slope, may be useful in confirming the diagnosis23 and may be required to
estimate the extent and severity of disease19,21,46 in
these patients.
Acknowledgments
We are indebted to Drs. Harvey L. Goldberg and
Jeffrey S. Borer for providing the angiographic
data.
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KEY WORDS * exercise tests * electrocardiography * oxygen
consumption * ischemia
Recovery-phase patterns of ST segment depression in the heart rate domain.
Identification of coronary artery disease by the rate-recovery loop.
P M Okin, O Ameisen and P Kligfield
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Circulation. 1989;80:533-541
doi: 10.1161/01.CIR.80.3.533
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