Download Diagnostic and Prognostic Value of Holter-Detected ST

Diagnostic and Prognostic Value of
Holter-Detected ST-Segment Deviation
in Unselected Patients With Chest Pain
Referred for Coronary Angiography*
A Long-term Follow-up Analysis
Chandra K. Nair, MD, FCCP; Ijaz A. Khan, MD; Dennis J. Esterbrooks, MD;
Kay L. Ryschon, MS; Daniel E. Hilleman, PharmD
Objective: To evaluate the diagnostic and prognostic significance of ST-segment deviation
detected by ambulatory Holter monitoring in unselected chest pain patients referred for
coronary angiography.
Methods: Two hundred seventy-seven patients (71% were men) who underwent coronary
angiography for evaluation of chest pain were studied with 24-h ambulatory Holter monitoring
within 72 h of angiography. A lumen diameter reduction of > 50% was considered coronary
artery disease. The ST-segment deviation was defined as > 1-mm deviation from the baseline
lasting > 1 min separated by a minimum of 1 min. The patients were followed up for 65 ⴞ 21
months (mean ⴞ SD) for occurrences of death, myocardial infarction, hospitalization for unstable
angina, and need for revascularization.
Results: Of the 277 patients, 223 (80%) had coronary artery disease. The prevalence of coronary
artery disease was not significantly different in patients with (43 of 48 patients; 90%) and without
(180 of 229 patients; 79%) Holter-detected ST-segment deviation. The diagnostic accuracy of
Holter-detected ST-segment deviation in predicting the presence of coronary artery disease was
poor (33%), with a sensitivity of 19% and a specificity of 91%. The presence of Holter-detected
ST-segment deviation was not predictive of future cardiac events or death.
Conclusion: The ST-segment changes detected on ambulatory Holter monitoring are of limited
value in identifying coronary artery disease and predicting the future adverse cardiac events or
death in unselected patients with chest pain.
(CHEST 2001; 120:834 – 839)
Key words: ambulatory ECG monitoring; coronary artery disease; diagnostic accuracy; ECG; Holter monitoring;
ischemic heart disease; sensitivity; silent ischemia; specificity; ST segment
Abbreviation: NS ⫽ not significant
deviation detected by ambulaT hetoryST-segment
ECG monitoring correlates well with the
other objective measures used to define myocardial
ischemia in patients with known coronary artery
disease.1–11 The presence of ST-segment deviation
during ambulatory ECG (Holter) monitoring in selected patients with stable angina pectoris, unstable
angina, myocardial infarction, and aborted sudden
cardiac death is also predictive of future cardiac
events.9 –16 However, limited data are available regarding the diagnostic and prognostic value of the
*From the Division of Cardiology, Department of Medicine,
Creighton University School of Medicine, Omaha, NE.
Manuscript received December 4, 2000; revision accepted March
21, 2001.
Correspondence to: Chandra K. Nair, MD, FCCP, Creighton
University Cardiac Center, 3006 Webster St, Omaha, NE 68131
Holter-detected ST-segment deviation in the unselected patients with chest pain referred for coronary
angiography. Similarly, the diagnostic significance of
the ST-segment deviation detected by ambulatory
ECG monitoring is unknown in patients with baseline ST-segment changes known to affect ST-T wave
interpretation, whereas exercise-induced ST-segment
deviation is known to have a lower diagnostic yield in
these patients.16
In this study, the diagnostic and prognostic significance of Holter-detected ST-segment deviation in
unselected patients with chest pain referred for
coronary angiography was determined, and was correlated with the extent and severity of coronary
artery disease. The diagnostic and prognostic significance of Holter-detected ST-segment deviation was
also compared between patients with baseline ST-
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Clinical Investigations
segment changes known to affect ST-T wave interpretation and those without such changes.
Materials and Methods
Patient Population
Two hundred seventy-seven consecutive patients with chest
pain referred for coronary angiography at the Creighton University Medical Center were enrolled in this prospective study. All
patients were characterized according to age, gender, history of
myocardial infarction, previous revascularization procedures,
standard risk factor assessment, concomitant disease status, drug
therapy, and angina history. Patients were instructed to continue
taking all of their medications, including digoxin and antianginal
medications, during ambulatory ECG monitoring.
Study Protocol
The study was approved by the Institutional Review Board for
Human Subjects Research of the Creighton University, and
written informed consent was obtained from all participants. All
study participants underwent continuous 24-h ambulatory ECG
monitoring within 72 h after the coronary angiography.
Coronary Angiography: Coronary angiography was performed
using the Judkin’s approach. Multiple coronary angiograms were
made in a variety of projections to ensure the lesion visibility and
accuracy. Coronary stenosis was assessed visually and interpreted
by two observers unaware of the results of the ambulatory ECG
recordings. Significant coronary stenosis was defined as a decrease in lumen diameter of ⱖ 50% in one or more of the major
epicardial coronary arteries or their primary branches.
Ambulatory Monitoring: Continuous 24-h ambulatory ECG
recordings were made on new ferrous oxide tapes using timecoded, reel-to-reel recorders (model 447; Delmar Avionics;
Irvine, CA). The frequency range from these amplitude-modified
recorders was 0.05 to 100 Hz. Calibration was accomplished with
1-mV and 0.1-mV square waves using a multiphase calibrator
simulating the ECG QRS-complex. A two-lead system (modified
lead II and V5) was used with meticulous skin preparation.
Electrode sites were verified for lead placement and signal
amplitude using a transtelephonic modulator transmitter. Subjects kept a detailed diary of the activities performed and
symptoms experienced during the 24-h monitoring period. Ambulatory ECG recordings were reviewed using a Cardio-Data
Prodigy Scanner (Mortara Instrument; Milwaukee, WI) at 120
times real time. Significant ST-segment depression or elevation
was defined as ⱖ 1 mm ST-segment deviation occurring 80 ms
after the J point, lasting for ⱖ 60 s. The episodes of ST-segment
deviation agreed on by two reviewers were considered as significant. Separation of one episode from another required that the
ECG return to baseline for a minimum of 1 min. The total
number of the ST-segment deviations and the total duration of
the episodes were determined for each patient. The heart rates at
the onset and at the time of maximal ST-segment deviation were
recorded for each individual episode. The physicians performing
ECG analyses were blinded to the coronary angiographic findings
and clinical characteristics of the patients.
Follow-up: Patients were prospectively followed up for a
mean ⫾ SD of 65 ⫾ 21 months from the time of initial monitoring for occurrences of death, nonfatal myocardial infarction,
hospitalization for unstable angina, and need for revascularization
with coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or any other transcatheter revascu-
larization procedure. Hospital records, outpatient clinic records,
and patient, family or primary physician’s interviews were used
for confirmation of the events. Deaths were classified as cardiac
or noncardiac. Myocardial infarction was diagnosed if two of the
following three prospectively defined criteria were met:
(1) ischemic type chest pain with duration ⬎ 20 min; (2) a
diagnostic ECG, which consisted of ST-segment elevation of ⱖ 1
mm in two or more anatomically contiguous leads or development of new left bundle branch block; (3) serum creatine
kinase-MB level of ⬎ 5 ng/mL with a creatine kinase-MB relative
index of ⬎ 2.5% in two consecutive serum samples. Unstable
angina was diagnosed if ischemic type chest pain lasted for ⬎ 20
min in absence of the ECG or enzyme changes consistent with
myocardial infarction.
Statistical Analysis
Data were presented as mean ⫾ SD where appropriate. A
statistical probability of ⬍ 0.05 was considered significant. The
diagnostic accuracy of the ST-segment deviation was examined
for all patients and for subgroups of patients with and without
baseline ST-segment changes. The prognostic value of the STsegment deviation was examined for all patients, Comparisons of
the groups with and without ST-segment deviation were performed using the Student’s t test or Pearson’s ␹2 where appropriate. All p values were corrected for multiple comparisons
where appropriate. The diagnostic value of the presence of the
ST-segment deviation for the detection of coronary artery disease
was evaluated by calculation of sensitivity, specificity, positive and
negative predictive values, and diagnostic accuracy. The following
calculations were used: sensitivity (%) ⫽ 100 ⫻ (true-positives)/
(true-positives ⫹ false-negatives); specificity (%) ⫽ 100 ⫻ (truenegative)/(true-negatives ⫹ false-positives); positive predictive
value (%) ⫽ 100 ⫻ (true-positives)/(true-positives ⫹ false-positives); and negative predictive value (%) ⫽ 100 ⫻ (true-negatives)/(true-negatives ⫹ false-negatives); and diagnostic accuracy
(%) ⫽ 100 ⫻ (true-positives ⫹ true-negatives/total number of
tests). All the statistical analyses were performed using computer
software (SPSS version 7.0; SPSS; Chicago, IL).
Results
Clinical Characteristics
The study group consisted of 277 patients (196
men), with a mean age of 63 ⫾ 10 years (range, 32 to
84 years). Clinical characteristics of the patients with
and without ST-segment deviation during Holter
monitoring are summarized in Table 1. The distribution of baseline characteristics was not different
between the two study groups. Seventy-one patients
had preexisting conditions affecting the ST segment;
44 patients were receiving digoxin, 1 patient had
complete left bundle-branch block, 8 patients had
left ventricular hypertrophy, 6 patients had permanent pacemakers implanted, and 12 patients had one
or more of the above.
Angiographic Findings
Two hundred twenty-three patients (80%) had at
least one vessel with ⱖ 50% obstruction, and 54
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Table 1—Baseline Clinical Characteristics of
Patients With and Without Holter-Detected
ST-Segment Deviation*
With ST-Segment
Without STDeviation
Segment Deviation
(n ⫽ 48)
(n ⫽ 229)
Characteristics
Age, yr
Men
Unstable angina
Prior myocardial infarction
Hypertension
Congestive heart failure
Diabetes mellitus
Hypercholesterolemia
Smoking
Active smoking at the time
of enrollment
Prior or active smoking at
the time of enrollment
65.6 ⫾ 11.4
33 (69)
6 (13)
6 (13)
22 (46)
7 (15)
12 (25)
19 (40)
62.9 ⫾ 10.2
163 (71)
37 (16)
28 (12)
117 (51)
30 (13)
32 (14)
84 (37)
6 (13)
45 (20)
27 (56)
151 (66)
*Data are presented as No. of patients (%) or mean ⫾ SD; p ⫽ NS
for all characteristics.
patients (20%) had no significant coronary obstruction. Single-vessel, double-vessel, and triple-vessel
disease was present in 92 patients (33%), 59 patients
(21%), and 72 patients (26%), respectively. The
prevalence of coronary artery disease in patients with
ST-segment deviation was not significantly different
than that in patients without ST-segment deviation
(43 of 48 patients [90%] vs 180 of 229 patients
[79%]; p ⫽ not significant [NS]). Similarly, there was
no significant difference in the single-vessel, doublevessel, and triple-vessel disease between groups (Table 2).
Ambulatory Holter ECG Findings
Forty-eight patients (17%) had one or more episodes of ST-segment deviation with a total of 120
episodes. Thirty-four patients had 90 episodes of
ST-segment depression, and 17 patients had 30
episodes of ST segment elevation. The average duration of episodes of ST depression was 42 ⫾ 60 min
Table 2—Coronary Angiographic Findings in
Patients With and Without Holter-Detected
ST-Segment Deviation*
Angiographic Findings
Coronary artery disease
Single-vessel disease
Double-vessel disease
Triple-vessel disease
Left main disease
With ST-Segment Without ST-Segment
Deviation (n ⫽ 48) Deviation (n ⫽ 229)
43 (90)
11 (23)
15 (31)
15 (31)
2 (4)
180 (79)
73 (32)
44 (19)
57 (25)
6 (3)
*Data are presented as No. of patients (%); p ⫽ NS for all angiographic findings.
Table 3—Diagnostic Accuracy of Holter-Detected STSegment Changes for Predicting Coronary Artery
Disease in all Patients*
Variables
Any ST-segment changes
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
ST-segment elevation
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
ST-segment depression
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
CAD
1
VD
2
VD
3
VD
19
91
90
21
33
13
91
69
40
44
25
91
75
53
57
21
91
75
46
51
7
98
94
20
25
6
98
83
40
42
12
98
88
51
53
4
98
75
43
44
14
93
88
21
29
10
93
67
40
42
15
93
69
50
52
17
93
75
46
49
*Data are presented as %; p ⫽ NS for all parameters. 1 VD ⫽ onevessel disease; 2 VD ⫽ two-vessel disease; 3 VD ⫽ three-vessel
disease; CAD ⫽ coronary artery disease.
(range, 1 to 272 min). The magnitude of ST-segment
depression ranged from 1.0 to 4.2 mm (mean,
2.0 ⫾ 0.8 mm), and it was ⱖ 1 mm in 21 patients and
ⱖ 2 mm in 13 patients. The average duration of
ST-segment elevation episodes was 17 ⫾ 21 min
(range, 2.5 to 75.5 min). Magnitude of ST-segment
elevation ranged from 1.0 to 6.0 mm (mean,
2.1 ⫾ 1.5 mm).
Diagnostic Accuracy of Holter-Detected
ST-Segment Deviation
The diagnostic accuracy of the ST-segment deviation detected by the ambulatory ECG monitoring in
predicting the presence of coronary artery disease
for all patients is given in Table 3, and in patients
with or without baseline ST-segment abnormalities
in Table 4. Of the 223 patients with coronary artery
disease, 43 patients (24%) had ST-segment changes.
Of the 54 patients without coronary artery disease, 5
patients (10%) had ST-segment changes. Correlation
of the Holter-detected ST-segment deviation and
the severity and location of obstructed coronary
arteries is shown in Table 5.
Prognostic Value of Holter-Detected
ST-Segment Deviation
Presence of any ST-segment deviation (depression
or elevation) was not significantly correlated with the
future cardiac events or death (Table 6). During a
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Clinical Investigations
Table 4 —Diagnostic Accuracy of Holter-Detected ST-Segment Changes for Predicting Coronary Disease in Patients
With vs Without Baseline ST-Segment Changes*
CAD
With
Any ST-segment change
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
ST-segment elevation
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
ST-segment depression
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Diagnostic accuracy
1 VD
Without
With
2 VD
Without
With
3 VD
Without
With
Without
31
92
95
23
30
15
90
86
21
42
18
92
75
46
42
12
90
67
39
50
41
92
88
55
54
19
90
67
52
63
32
92
88
44
49
16
90
67
47
54
9
92
83
19
25
7
100
100
21
24
6
92
50
43
42
6
100
100
39
43
18
92
75
46
54
10
100
100
52
50
5
92
50
36
47
4
100
100
46
37
22
100
100
22
26
10
90
81
20
37
12
100
100
46
40
9
90
60
38
50
24
100
100
50
51
12
90
56
50
57
27
100
100
45
47
12
90
60
46
54
*Data are presented as %; p ⫽ NS for all parameters. See Table 3 for expansion of abbreviations.
mean follow-up of 65 ⫾ 21 months, the incidence of
cardiac events (cardiac death, nonfatal myocardial
infarctions, hospitalization for unstable angina, and
need for revascularization) was similar in patients
with and without ST-segment deviation, and was not
a function of presence or absence of baseline STsegment abnormalities.
Discussion
Experience with ambulatory ECG monitoring for
myocardial ischemia has been associated with a
highly variable sensitivity and specificity for the
detection of coronary artery disease.1–16 The STsegment changes consistent with ischemia have been
observed during ambulatory ECG monitoring in 18
to 59% of the patients with known coronary artery
disease, and have generally correlated well with the
other objective tests used to detect myocardial ischemia.13–21 The highest prevalence of ambulatory
ECG monitoring detected ST-segment changes have
been reported in patients with multivessel disease,
unstable angina, or a recent myocardial infarction.22–29 However, the diagnostic accuracy of the
exercise stress testing in the patients with coronary
artery disease is significantly greater than that observed with the ambulatory ECG monitoring.17 The
sensitivity of the ambulatory ECG monitoring-detected ST-segment changes for detection of myocardial ischemia is low even in patients with triple-vessel
Table 5—Correlation of Holter-Detected ST-Segment Changes With Severity of Disease and Coronary
Artery Involved*
Variables
Severity of coronary stenosis
ⱖ 50% and ⬍ 75%
ⱖ 75% and ⬍ 90%
ⱖ 90%
Location of coronary artery stenosis
LM
LAD/DIAG
LCX/OM
RCA/PDA
Any ST-Segment
Change
ST-Segment
Elevation
ST-Segment
Depression
2/30 (7)
6/31 (19)
36/161 (22)
1/30 (3)
4/31 (13)
11/161 (7)
1/30 (3)
2/31 (7)
28/161 (17)
5/24
17/72
15/55
6/34
(21)
(24)
(27)
(18)
2/24 (8)
8/72 (11)
5/55 (9)
2/34 (6)
3/24
10/72
11/55
4/34
(13)
(14)
(20)
(12)
*Data are presented as No. of patients/total (%); p ⫽ NS for all parameters. LM ⫽ left main; LAD/DIAG ⫽ left anterior descending/diagonal;
LCX/OM ⫽ left circumflex/obtuse marginal; RCA/PDA ⫽ right coronary artery/posterior descending artery.
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Table 6 —Correlation of Presence or Absence of Holter-Detected ST-Segment Changes With Adverse
Cardiovascular Outcomes*
Variables
Cardiac
Death
Myocardial
Infarction
CABG
PTCA
Unstable
Angina
Combined
Outcomes
Any ST-segment deviation
No ST-segment deviation
ST-segment elevation ⬎ 1 mm
ST-segment depression ⬎ 1 mm
7/48 (15)
23/229 (10)
2/17 (12)
5/34 (15)
6/48 (13)
28/229 (12)
4/17 (24)
3/34 (9)
9/48 (19)
29/229 (13)
3/17 (18)
6/34 (18)
8/48 (17)
36/229 (16)
4/17 (24)
5/34 (15)
6/48 (13)
37/229 (16)
3/17 (18)
3/34 (9)
23/48 (48)
101/229 (44)
10/17 (59)
15/34 (44)
*Data are presented as No. of patients/total (%); p ⫽ NS for all correlations; CABG ⫽ coronary artery bypass grafting; PTCA ⫽ percutaneous
transluminal coronary angioplasty.
or left main coronary artery disease. Presumably, this
is because these patients are relatively inactive to
avoid angina, and so their heart rates (and double
products) are relatively low. This is undoubtedly a
major limitation of ambulatory ECG monitoring as
opposed to exercise stress testing in detecting myocardial ischemia.
The prevalence of the ST-segment changes detected during the ambulatory ECG monitoring in
our patients with coronary artery disease was 24%.
Although the specificities were high, the sensitivities
and diagnostic accuracy of the ST-segment change
during ambulatory ECG monitoring in our population were poor. This is generally consistent with
other published reports.12–21 In our study, however,
the presence of multivessel disease, unstable angina,
or myocardial infarction was not associated with a
higher prevalence of ambulatory ECG monitoring
detected ST-segment changes, and ambulatory ECG
monitoring also failed to predict the severity and
location of the coronary artery stenosis, which is in
discrepancy with some other published reports.12–21
These discrepancies between the results of our study
and with other published reports may be due to the
fact that our patient population consisted of unselected patients of chest pain.
Despite the relatively poor and erratic diagnostic
value of the ambulatory ECG monitoring, the presence of the Holter-detected ST-segment changes in
certain patient populations is highly predictive of
future adverse cardiac events. In patients with stable
angina, ST-segment changes detected by ambulatory
ECG monitoring is an independent predictor of the
adverse clinical events including death, myocardial
infarction, and revascularization.12–21 In addition, the
ambulatory ECG monitoring provides prognostic
information additional to that derived from the
established parameters obtained during exercise
testing.13,18,29 Ischemia detected by the ambulatory
ECG monitoring in patients with unstable angina or
myocardial infarction has also been shown to be
predictive of the future adverse clinical outcomes.25–29 However, the presence of ST-segment
changes in our population was not predictive of
future adverse clinical outcomes. We believe this
occurred as our population consisted of unselected
patients with chest pain.
Conclusion
The ST-segment changes detected on ambulatory
ECG monitoring in unselected patients with chest
pain are of limited value in identifying the coronary
artery disease and predicting the future adverse
cardiac events including death, myocardial infarction, need for hospitalization for unstable angina, and
revascularization.
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