- Email: [email protected]
Quantitative relation of ST-segment depression during exercise to the magnitude of myocardial ischemia as assessed by single-photon emission computed tomographic myocardial perfusion imaging
Quantitative Relation of ST-Segment Depression During Exercise to the Magnitude of Myocardial Ischemia as Assessed by Single-Photon Emission Computed Tomographic Myocardial Perfusion Imaging Thomas H. Hauser,
MD,
Sharmila Dorbala, MD, Abdulbaset Sulaiman, Marcelo F. Di Carli, MD
MD,
and
The mechanism of ST-segment depression during exercise electrocardiographic treadmill testing (ETT) is unknown. The relatively good correlation between the results of ETT and myocardial perfusion imaging suggests that ST-segment depression may be related to the magnitude of ischemia. Previous studies that investigated this relation have produced conflicting results. We evaluated 1,006 patients who underwent symptom-limited ETT and technetium-99m single-photon emission computed tomographic myocardial perfusion imaging at rest and during stress at a single institution. The magnitude, extent, and duration of ST-segment depression were each strongly associated with the magnitude of myocardial
ischemia (p <0.001 for all). The magnitude, extent, and duration of ST-segment depression were highly correlated with each other and had similar relations to the magnitude of ischemia. After adjustment for significant clinical and ETT parameters, these relations remained highly significant. The location of myocardial ischemia was unrelated to ST-segment depression. This large study found that ST-segment depression during ETT is strongly associated with the magnitude of ischemia. These data support a causative role for the magnitude of ischemia in the generation of ST-segment depression. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:703–708)
xercise electrocardiographic treadmill testing (ETT) and single-photon emission computed toE mographic (SPECT) myocardial perfusion imaging
the magnitude of ischemia, we prospectively evaluated 1,006 patients who underwent ETT and technetium-99m SPECT myocardial perfusion imaging.
are frequently combined for the detection of myocardial ischemia in patients with known or suspected coronary artery disease (CAD). The 2 tests have proved useful for detection of CAD and prediction of adverse outcomes associated with CAD.1,2 Although the mechanism of ST-segment depression is unknown, the relatively good correlation between ETT and myocardial perfusion imaging suggests that ST-segment depression may be related to the global magnitude of ischemia.3–5 Previous attempts to directly address this hypothesis have produced conflicting results.6 –11 In addition, an alternative hypothesis that suggests that greater global ischemia results in less ST-segment depression has been proposed.12–14 To further investigate the relation between ST-segment depression and From the Division of Nuclear Medicine, Department of Radiology, Brigham and Women’s Hospital; the Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center; and Harvard Medical School, Boston, Massachusetts. Dr. Hauser is a fellow in the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center, Harvard/MIT Health Sciences and Technology, Boston, Massachusetts in collaboration with Pfizer Inc., New York, New York. Manuscript received February 13, 2004; revised manuscript received and accepted June 7, 2004. Address for reprints: Marcelo F. Di Carli, Brigham and Women’s Hospital, Division of Nuclear Medicine, 75 Francis Street, Boston, Massachusetts. E-mail: [email protected]. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 September 15, 2004
METHODS
Study cohort: All patients who underwent ETT and gated technetium-99m SPECT myocardial perfusion imaging at rest and during stress at a single institution from March to November 2002 were considered for entry into the study cohort. Patients with left ventricular hypertrophy, ST-segment depression, or left bundle branch block on their baseline electrocardiogram or with ST-segment elevation during exercise were excluded. A structured interview and review of medical records were performed before ETT to obtain relevant clinical data. ETT protocol: All patients in the study cohort underwent symptom-limited ETT according to a standard Bruce protocol.15 Electrocardiographic and hemodynamic data were obtained during exercise and recovery. One cardiologist (SD or MFDC) reviewed the electrocardiographic data for each electrocardiographic treadmill test, and the maximal ST-segment depression in any lead 80 ms after the J point was recorded. ST-segment depression that was ⬍1 mm or rapidly upsloping was disregarded. In addition, the number of leads with ST-segment depression, the duration of ST-segment depression, the heart rate at the onset of ST-segment depression, and the exercise duration before ST-segment depression were recorded. 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.06.001
703
TABLE 1 Characteristics of the Study Patients Magnitude of Ischemia Characteristic Men Age (yrs) Body mass index (kg/m2) Chest pain Typical chest pain Dyslipidemia Hypertension Diabetes mellitus Tobacco use Percutaneous coronary revascularization Myocardial infarction Surgical coronary revascularization Medication usage Aspirin  Antagonist Statin ACE inhibitor Diuretic Calcium-2⫹ receptor antagonist Dihydropyridine class Long-acting nitrate
Total (n ⫽ 1,006)
None (n ⫽ 701)
Mild (n ⫽ 109)
Moderate (n ⫽ 135)
Severe (n ⫽ 61)
p Value*
613 (60.9%) 59 ⫾ 11 28.3 ⫾ 5.5 532 (52.9%) 357 (35.5%) 624 (62.0%) 610 (60.6%) 171 (17.0%) 123 (12.2%) 279 (27.7%) 196 (19.5%) 142 (14.1%)
370 (53%) 58 ⫾ 12 28.2 ⫾ 5.3 365 (52%) 235 (34%) 395 (56%) 412 (59%) 102 (15%) 84 (12%) 150 (21%) 93 (13%) 65 (9%)
81 (74%) 61 ⫾ 12 28.2 ⫾ 5.0 56 (51%) 29 (27%) 81 (74%) 74 (68%) 22 (20%) 15 (14%) 43 (39%) 45 (41%) 31 (28%)
114 (84%) 62 ⫾ 10 28.3 ⫾ 5.8 71 (52%) 60 (44%) 103 (76%) 80 (59%) 32 (24%) 19 (14%) 62 (46%) 44 (33%) 36 (27%)
48 (79%) 60 ⫾ 10 30.0 ⫾ 6.7 41 (67%) 33 (54%) 45 (75%) 44 (72%) 15 (25%) 5 (8%) 24 (39%) 14 (23%) 10 (16%)
⬍0.001 0.009 0.098 0.145 ⬍0.001 ⬍0.001 0.075 0.014 0.653 ⬍0.001 ⬍0.001 ⬍0.001
574 561 554 362 160 106 62 75
372 343 341 227 119 77 43 38
(57.1%) (55.8%) (55.1%) (36.0%) (15.9%) (10.5%) (6.2%) (7.5%)
(53%) (49%) (49%) (32%) (17%) (11%) (6%) (5%)
73 73 73 48 14 8 4 9
(67%) (67%) (67%) (44%) (13%) (8%) (4%) (8%)
93 98 96 62 21 16 12 16
(69%) (73%) (71%) (46%) (16%) (12%) (9%) (12%)
36 47 44 25 6 4 3 12
(59%) (77%) (72%) (41%) (10%) (7%) (5%) (20%)
⬍0.001 ⬍0.001 ⬍0.001 0.004 0.383 0.568 0.381 ⬍0.001
*The p value is reported for the association with increasing magnitude of ischemia. ACE ⫽ angiotensin-converting enzyme.
Protocol for myocardial perfusion imaging: Patients were injected with 8 to 13 mCi technetium-99m sestamibi (Cardiolite, Bristol-Myers Squibb Imaging Inc., North Billerica, Massachusetts) at rest, and gated SPECT imaging was initiated 15 to 30 minutes later with a 3-detector (Prism 3000, Picker International Inc., Bedford Heights, Ohio) or 2-detector (e.cam duet, Siemens Medical Solutions, Hoffman Estates, Illinois) gamma camera. During maximal exercise, patients were injected with 25 to 35 mCi technetium-99m sestamibi and then exercised for an additional 60 seconds. Gated SPECT imaging was initiated 15 to 30 minutes later on the same gamma camera. Images were transferred to a dedicated workstation and analyzed by using standard, commercially available software (e.soft, Siemens Medical Solutions). Tomographic images were reconstructed by using filtered backprojection with a Butterworth filter (power 5, cut-off frequency 0.79 cycles/pixel). Gated images were reconstructed in the same manner with 8 frames per cardiac cycle. One nuclear cardiologist (SD or MFDC) reviewed each myocardial perfusion image. A 17-segment, 5-point (0 ⫽ normal uptake, 4 ⫽ absent uptake) scoring system was used to compute a summed stress score, summed rest score, and summed difference score. In patients with abnormal images (summed stress score ⬎3), the magnitude of ischemia was classified as none (summed difference score 0), mild (1 to 3), moderate (4 to 7), or severe (ⱖ8). The magnitude of fixed defects was classified as none (summed difference score 0), mild (1 to 3), moderate (4 to 7), or severe (ⱖ8). Each segment was assigned to a coronary arterial territory based on a generally accepted standard.16 Statistical analysis: Numerical data are presented as mean ⫾ SD. Data for the summed data score were skewed and are reported as the mean, median, and 704 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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interquartile range (25th to 75th percentile). Categorical and ordinal data are presented as counts and percentages, respectively. The relation of clinical characteristics and ETT parameters to the results of myocardial perfusion imaging were analyzed with the chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests. Analysis of the relation of ST-segment depression to the location of ischemia was restricted to those patients with ischemia limited to a single vascular territory. Adjustment of the relation between ST-segment depression and the severity of ischemia was performed with ordinal logistic regression, including all variables with a univariate p value ⬍0.2. The relations between different parameters of ST-segment depression were evaluated with Spearman’s correlation. Statistical analysis was performed with SAS 8.2 for Windows (SAS Institute, Cary, North Carolina).
RESULTS
Characteristics of the study cohort: A total of 1,006 patients was included in the study cohort. Clinical characteristics and ETT parameters of the study cohort are shown in Tables 1 and 2, respectively. Quantitative relation of ST-segment depression to the magnitude of ischemia on myocardial perfusion imaging:
ST-segment depression was present in 232 patients (23%), and ischemia was present in 305 patients (30%). ST-segment depression was present without ischemia in 107 patients (11%), and ischemia was present without ST-segment depression in 180 patients (18%). The presence of ST-segment depression was strongly associated with an increasing magnitude of ischemia (p ⬍0.001; Table 2). After adjustment for potential confounders, the association remained highly significant (p ⬍0.001). There was no significant association between the presSEPTEMBER 15, 2004
TABLE 2 Exercise Treadmill Test Parameters Magnitude of Ischemia Parameter Baseline electrocardiogram Nonspecific T-wave changes Right bundle branch block Left atrial abnormality Previous myocardial infarction Anterior Inferior Lateral Exercise Heart rate at rest (beats/min) Systolic blood pressure at rest (mm Hg) Diastolic blood pressure at rest (mm Hg) Peak heart rate (beats/min) Peak systolic blood pressure (mm Hg) Exercise duration (min) Symptoms Chest pain Dyspnea Reason for termination Fatigue Chest pain Hypertensive response Marked STD Hypotension Other STD (ⱖ1 mm) Maximal heart rate without STD (beats/min) Maximal exercise duration without STD (min)
Total (n ⫽ 1,006)
None (n ⫽ 701)
Mild (n ⫽ 109)
278 72 29 95 54 49 13
(28%) (7%) (3%) (9%) (5%) (5%) (1%)
175 (25%) 45 (6%) 21 (2%) 35 (5%) 24 (3%) 13 (2%) 3 (⬍1%)
41 9 2 31 14 18 5
66 129 78 138 186 8.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
67 129 79 141 188 8.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
65 128 78 135 182 7.8
24 17 9 22 24 2.9
27 16 9 22 23 2.9
(38%) (8%) (2%) (28%) (13%) (17%) (5%) ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
12 17 8 23 29 3.0
195 (19%) 230 (23%)
102 (15%) 151 (15%)
22 (20%) 29 (27%)
849 (84%) 66 (7%) 33 (3%) 25 (3%) 11 (1%) 52 (5%) 232 (23%) 135 ⫾ 23 7.4 ⫾ 3.1
609 (87%) 32 (5%) 29 (4%) 8 (1%) 4 (1%) 35 (5%) 107 (15%) 139 ⫾ 23 7.7 ⫾ 3.0
85 (87%) 4 (4%) 2 (2%) 2 (2%) 1 (1%) 5 (5%) 26 (24%) 131 ⫾ 24 7.3 ⫾ 3.2
Moderate (n ⫽ 135) 45 13 5 24 13 13 5 64 127 77 130 181 7.9
(33%) (10%) (4%) (18%) (10%) (10%) (4%) ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
11 20 9 20 25 2.9
43 (32%) 38 (28%) 108 (80%) 16 (12%) 1 (1%) 7 (5%) 4 (3%) 9 (7%) 57 (42%) 124 ⫾ 20 6.8 ⫾ 2.9
Severe (n ⫽ 61) 17 5 1 5 3 2
68 135 81 132 182 7.6
p Value*
(28%) (8%) (2%) (8%) (5%) (3%) 0
0.018 0.549 0.772 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
0.639 0.017 0.005 ⬍0.001 0.006 0.556
13 19 8 17 29 3.1
28 (46%) 12 (20%)
⬍0.001 0.256
37 (61%) 14 (23%) 1 (2%) 8 (13%) 2 (3%) 3 (5%) 42 (69%) 124 ⫾ 20 5.9 ⫾ 3.1
⬍0.001 ⬍0.001 0.133 ⬍0.001 0.031 0.863 ⬍0.001 ⬍0.001 ⬍0.001
*The p value is reported for the association with increasing magnitude of ischemia. STD ⫽ ST-segment depression.
ence of ST-segment depression and the magnitude of fixed defects (p ⫽ 0.543). The relation between ST-segment depression and the magnitude of ischemia was further evaluated by stratifying the magnitude, extent, and duration of STsegment depression (Figure 1). Increasing magnitudes of ischemia were associated with more frequent, more severe, more extensive, and more prolonged ST-segment depression (p ⬍0.001 for all). Conversely, increased magnitude, extent, and duration of ST-segment depression were associated with increased ischemia (p ⬍0.001 for all; Table 3). The magnitude, extent, and duration of ST-segment depression were highly correlated with each other (r ⬎0.99, p ⬍0.001 for all) and displayed similar relations to the magnitude of ischemia. There was no statistically significant association of any measure of ST-segment depression with fixed defects (Table 3). Adjusted odds ratios were calculated for the association of ST-segment depression with increasing magnitude of ischemia. At each break point on the ischemia scale, the odds ratio represents the probability of a patient belonging to the group with greater ischemia as opposed to the probability of belonging to the group with less ischemia. The magnitude, extent, and duration of STsegment depression were strongly associated with increasing ischemia at each break point on the ischemia scale (p ⬍0.001; Figure 2). The association was greatest with severe ischemia (summed difference score ⱖ8) and
for ST-segment depression ⱖ2 mm, in ⱖ6 leads, or for ⱖ7 minutes. Of all variables measured, the magnitude, extent, and duration of ST-segment depression showed the strongest relation to the magnitude of ischemia. The maximal value of R2 for any of the models was ⬍0.35.
Relation of the magnitude of ST-segment depression to the location of ischemia: Of the 305 patients in the
study cohort with ischemia, 153 (50%) had ischemia confined to a single coronary arterial territory, 118 (39%) had ischemia in 2 coronary arterial territories, and 34 (11%) had ischemia in all 3 coronary arterial territories. The magnitude of ST-segment depression increased progressively with the number of coronary arterial territories involved (p ⫽ 0.007; Figure 3). Of those with ischemia in a single coronary arterial territory, 51 (33%) had ischemia in the usual left anterior descending coronary artery territory, 32 (21%) had ischemia in the usual left circumflex coronary artery territory, and 70 (46%) had ischemia in the usual right coronary artery territory. There was no significant association of the location of ischemia and the magnitude of ST-segment depression (p ⬎0.10; Figure 4). Data for the extent and duration of ST-segment depression were similar.
DISCUSSION We found a strong and highly statistically significant positive association between ST-segment depression during ETT and the global magnitude of ischemia
CORONARY ARTERY DISEASE/MECHANISM OF ST-SEGMENT DEPRESSION
705
FIGURE 1. The prevalence, magnitude (A), extent (B), and duration (C) of ST-segment depression (STD) increases with increasing magnitude of ischemia, and the proportion of patients with no STD decreases as the magnitude of ischemia increases (p <0.001 for all).
as assessed by technetium-99m SPECT myocardial perfusion imaging. The magnitude, extent, and duration of ST-segment depression were highly correlated with each other and had similar relations to the magnitude of ischemia. After adjustment for all significant clinical and ETT parameters, these relations remained strongly significant. The presence of ST-segment depression ⱖ1 mm during ETT is commonly used for the diagnosis of CAD and predicts the occurrence of adverse events associated with CAD.2 The mechanism for the development of ST-segment depression during ETT is incompletely understood but is believed to be an electrical manifestation of underlying myocardial 706 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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ischemia. The presence and number of reversible perfusion defects found during myocardial perfusion imaging are also valuable for the diagnosis of CAD.1 ETT is often performed contemporaneously with myocardial perfusion imaging, and the results of the tests are usually concordant but discordant often enough to question the true relation of ST-segment depression to ischemia.3–5 Several previous studies have investigated this relation with different results.6 –10 Three smaller studies using thallium-201 myocardial perfusion imaging, 2 using planar imaging,7,8 and 1 using SPECT imaging11 found an insignificant or no relation of the magnitude of ST-segment depression to the magnitude of ischemia, even in patients with profound ST-segment depression.7 One study using technetium-99m SPECT myocardial perfusion imaging associated larger perfusion defects with an increased magnitude of ST-segment depression only among patients who had STsegment depression during ETT, thus excluding those with ischemia but no ST-segment depression,6 whereas another found that the magnitude of STsegment depression was not a good predictor of ischemia.10 We evaluated a large cohort of patients who underwent contemporaneous ETT and technetium-99m myocardial perfusion imaging and found that there was a highly statistically significant increase in the magnitude of ischemia in patients with ST-segment depression (Table 3). Moreover, the prevalence and magnitude of ST-segment depression increased uniformly with the magnitude of ischemia (p ⬍0.001; Figure 1). The previous negative studies were likely underpowered due to small sample sizes, but an additional factor may have been the improved imaging characteristics of technetium-99m versus those of thallium-201. The relation between ischemia and the extent and duration of ST-segment depression has been little studied. One study found that the extent of ST-segment depression was significantly associated with ischemia,6 whereas another found no relation between ischemia and the duration of ST-segment depression. We found that the extent and duration of ST-segment depression were highly correlated with each other (r ⬎0.99, p ⬍0.001 for all) and had similar, strong relations to the magnitude of ischemia (p ⬍0.001 for all; Figure 1 and Table 3). After adjustment for all potential confounders, the relation between ischemia and the magnitude, extent, and duration of ST-segment depression remained similar and highly statistically significant (p ⬍0.001 for all; Figure 2) and demonstrated the strongest relation of any of the variables tested. These results and the high correlation of the magnitude, extent, and duration of ST-segment depression with each other strongly suggest that these measures of ST-segment depression reflect a common underlying phenomenon that is ischemia or the result of ischemia. However, the relatively modest R2 value suggests that other significant causative factors remain to be elucidated. An alternative relation between ST-segment deSEPTEMBER 15, 2004
TABLE 3 Relation Between Indexes of ST-Segment Depression and Summed Difference Score Summed Difference Score Variable
n (%)
Mean
Median
IQR
No ST-segment depression ST-segment depression ⬍2 mm ⱖ2 mm In ⬍6 leads In ⱖ6 leads ⬍7 min ⱖ7 min
774 (77%)
1.0
0
0–0
130 102 84 147 120 112
2.3 5.1 2.7 4.0 2.6 4.5
0 4 0 3 0 4
0–4 0–8 0–4 0–7 0–4 0–7
(13%) (10%) (8%) (15%) (12%) (11%)
Summed Rest Score p Value
⬍0.001 ⬍0.001 ⬍0.001
Mean
Median
IQR
2.6
1
0–3
1.9 3.1 2.5 2.4 1.8 3.0
1 2 1 1 1 1
0–2 0–4 0–4 0–4 0–2 0–4
p Value
0.060 0.472 0.156
IQR ⫽ interquartile range.
FIGURE 3. The relation between the magnitude of ST-segment depression (STD) and the number of coronary arterial territories with ischemia. The magnitude of STD progressively increases as the number of coronary arterial territories with ischemia increases (p ⴝ 0.007).
FIGURE 2. Adjusted odds ratios for the association of the magnitude, extent, and duration of STD with ischemia. Each data point represents the odds ratio for having increased ischemia versus with less ischemia at each break point in the ischemia magnitude scale. None (N) 3 mild (m) moderate (M) severe (S) ⴝ odds ratio for having mild, moderate, or severe ischemia versus no ischemia; N m 3 M S ⴝ odds ratio for having moderate or severe ischemia versus no or mild ischemia; N m M 3 S ⴝ odds ratio for having severe ischemia versus no, mild, or moderate ischemia. Adjusted odds ratios account for all significant clinical and ETT parameters. Other abbreviation as in Figure 1.
pression and ischemia has been proposed in which the magnitude of ST-segment depression decreases with increasing ischemia because the electrical forces from ischemia in opposing walls negate each other and result in less ST-segment depression than does ischemia in a single territory.12–14 Previous investigations have shown an increased prevalence of ST-segment depression with increased severity of CAD.2 We found that increasing prevalence, magnitude, extent, and duration of ST-segment depression were positively associated with the number of coronary arterial territories involved (Figure 3), suggesting that the association between ST-segment depression and the magnitude of ischemia is not affected by cancellation of electrical forces.
Several previous studies have shown that there is little relation between the location of ischemia and the presence and magnitude of ST-segment depression during ETT.6,17–19 The results of our investigation are consistent with these findings. Given the large number of patients in our study cohort, there were large numbers of clinical and ETT parameters that were associated with increasing ischemia (Tables 1 and 2). Evidence of previous CAD, established risk factors for CAD, medication use for the treatment of CAD, and evidence of a positive ETT had the most consistent associations with the magnitude of ischemia. The ability to exercise to the point of fatigue without other symptoms or achieve a high rate–pressure product was protective. We did not use invasive coronary angiography to determine the extent of CAD. Although invasive coronary angiography is superior for the diagnosis of CAD, the semiquantitative method that we used to determine the magnitude of ischemia is commonly used, straightforward to determine, and provides more direct information about myocardial ischemia than about epicardial coronary disease that, in the presence of previous infarction, may not necessarily result in ischemia. We limited our study population to those patients who were able to exercise and had a diagnos-
CORONARY ARTERY DISEASE/MECHANISM OF ST-SEGMENT DEPRESSION
707
5. Vanzetto G, Ormezzano O, Fagret D, Comet M, Denis B, Machecourt J.
FIGURE 4. Relation of the magnitude of STD to the location of ischemia. Among patients with ischemia confined to a single coronary arterial territory, the association between the magnitude of STD and the location of ischemia was not significant (p >0.1). LAD ⴝ left anterior descending coronary artery, LCx ⴝ left circumflex coronary artery, RCA ⴝ right coronary artery. Other abbreviation as in Figure 1.
tic baseline electrocardiogram. As with all studies involving diagnostic tests, our results may have been affected by referral bias. 1. Beller GA, Zaret BL. Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease. Circulation 2000;101:1465– 1478. 2. Tavel ME. Stress testing in cardiac evaluation. Chest 2001;119:907–925. 3. Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Exercise myocardial perfustion SPECT in patients without known coronary artery disease. Circulation 1996;93:905–914. 4. Hachamovitch R, Berman DS, Kiat H, Cohen I, Friedman JD, Shaw LJ. Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms. Circulation 2002;205:823– 829.
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Long-term additive prognostic value of thallium-201 myocardial perfusion imaging over clinical and exercise stress test in low to intermediate risk patients. Circulation 1999;100:1521–1527. 6. Tavel ME, Shaar C. Relation between the electrocardiographic stress test and degree and location of myocardial ischemia. Am J Cardiol 1999;84:119 –124. 7. Colby J, Hakki AH, Iskandrian AS, Mattleman S. Hemodynamic, angiographic and scintigraphic correlates of positive exercise electrocardiograms: emphasis on strongly positive electrocardiograms. J Am Coll Cardiol 1983;2:21–29. 8. Taylor AJ, Sackett MC, Beller GA. The degree of ST-segment depression on symptom-limited exercise testing: relation to the myocardial ischemic burden as determined by thallium-201 scintigraphy. Am J Cardiol 1995;75:228 –231. 9. Bogaty P, Gavrielides S, Mure P, Gaspardone A, Maseri A. Duration and magnitude of ST-segment depression during exercise and recovery: a symmetric relation. Am Heart J 1995;129:666 – 671. 10. Galassi AR, Azzarelli S, Lupo L, Mammana C, Foti R, Tamburino C, Musumeci S, Giuffrida G. Accuracy of exercise testing in the assessment of the severity of myocardial ischemia as determined by means of technetium-99m tetrofosmin SPECT scintigraphy. J Nucl Cardiol 2000;7:575–583. 11. Bogaty P, Guimond J, Robitaille NM, Rousseau L, Simard S, Rouleau JR, Dagenais GR. A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates. J Am Coll Cardiol 1997;29:1497–1504. 12. Madias JE, Mahjoub M, Valance J. The paradox of negative exercise stress ECG/positive thallium scintigram. Ischemic ST-segment counterpoise as the underlying mechanism. J Electrocardiol 1996;29:243–248. 13. Madias JE, Khan M, Manyam B. The role of “ischemic ST-segment counterpoise” in rendering the response of exercise electrocardiogram falsely negative. Clin Cardiol 1997;20:489 – 492. 14. Madias JE, Knez P, Win MT. True-positive exercise electrocardiogram/falsenegative thallium-201 scintigram: a proposal of a mechanism for the paradox. Clin Cardiol 2000;23:625– 629. 15. Bruce RA, Hornsten TR. Exercise stress testing in evaluation of patients with ischemic heart disease. Prog Cardiovasc Dis 1969;11:371–390. 16. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. Circulation 2002;105:539 –542. 17. Dunn RF, Freedman B, Bailey IK, Uren RF, Kelly DT. Localization of coronary artery disease with exercise electrocardiography: correlation wit thallium-201 myocardial perfusion scanning. Am J Cardiol 1981;48:837– 843. 18. Fuchs RM, Achuff SC, Grunwald L, Yin FC, Griffith LS. Electrocardiographic localization of coronary artery narrowings: studies during myocardial ischemia and infarction in patients with one-vessel disease. Circulation 1982;66: 1168 –1176. 19. Kang X, Berman DS, Lewin HC, Miranda R, Agafitei R, Cohen I, Friedman JD, Germano G. Comparative localization of myocardial ischemia by exercise electrocardiography and myocardial perfusion SPECT. J Nucl Cardiol 2000;7: 140 –145.
SEPTEMBER 15, 2004
MD,
Sharmila Dorbala, MD, Abdulbaset Sulaiman, Marcelo F. Di Carli, MD
MD,
and
The mechanism of ST-segment depression during exercise electrocardiographic treadmill testing (ETT) is unknown. The relatively good correlation between the results of ETT and myocardial perfusion imaging suggests that ST-segment depression may be related to the magnitude of ischemia. Previous studies that investigated this relation have produced conflicting results. We evaluated 1,006 patients who underwent symptom-limited ETT and technetium-99m single-photon emission computed tomographic myocardial perfusion imaging at rest and during stress at a single institution. The magnitude, extent, and duration of ST-segment depression were each strongly associated with the magnitude of myocardial
ischemia (p <0.001 for all). The magnitude, extent, and duration of ST-segment depression were highly correlated with each other and had similar relations to the magnitude of ischemia. After adjustment for significant clinical and ETT parameters, these relations remained highly significant. The location of myocardial ischemia was unrelated to ST-segment depression. This large study found that ST-segment depression during ETT is strongly associated with the magnitude of ischemia. These data support a causative role for the magnitude of ischemia in the generation of ST-segment depression. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:703–708)
xercise electrocardiographic treadmill testing (ETT) and single-photon emission computed toE mographic (SPECT) myocardial perfusion imaging
the magnitude of ischemia, we prospectively evaluated 1,006 patients who underwent ETT and technetium-99m SPECT myocardial perfusion imaging.
are frequently combined for the detection of myocardial ischemia in patients with known or suspected coronary artery disease (CAD). The 2 tests have proved useful for detection of CAD and prediction of adverse outcomes associated with CAD.1,2 Although the mechanism of ST-segment depression is unknown, the relatively good correlation between ETT and myocardial perfusion imaging suggests that ST-segment depression may be related to the global magnitude of ischemia.3–5 Previous attempts to directly address this hypothesis have produced conflicting results.6 –11 In addition, an alternative hypothesis that suggests that greater global ischemia results in less ST-segment depression has been proposed.12–14 To further investigate the relation between ST-segment depression and From the Division of Nuclear Medicine, Department of Radiology, Brigham and Women’s Hospital; the Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center; and Harvard Medical School, Boston, Massachusetts. Dr. Hauser is a fellow in the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center, Harvard/MIT Health Sciences and Technology, Boston, Massachusetts in collaboration with Pfizer Inc., New York, New York. Manuscript received February 13, 2004; revised manuscript received and accepted June 7, 2004. Address for reprints: Marcelo F. Di Carli, Brigham and Women’s Hospital, Division of Nuclear Medicine, 75 Francis Street, Boston, Massachusetts. E-mail: [email protected]. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 September 15, 2004
METHODS
Study cohort: All patients who underwent ETT and gated technetium-99m SPECT myocardial perfusion imaging at rest and during stress at a single institution from March to November 2002 were considered for entry into the study cohort. Patients with left ventricular hypertrophy, ST-segment depression, or left bundle branch block on their baseline electrocardiogram or with ST-segment elevation during exercise were excluded. A structured interview and review of medical records were performed before ETT to obtain relevant clinical data. ETT protocol: All patients in the study cohort underwent symptom-limited ETT according to a standard Bruce protocol.15 Electrocardiographic and hemodynamic data were obtained during exercise and recovery. One cardiologist (SD or MFDC) reviewed the electrocardiographic data for each electrocardiographic treadmill test, and the maximal ST-segment depression in any lead 80 ms after the J point was recorded. ST-segment depression that was ⬍1 mm or rapidly upsloping was disregarded. In addition, the number of leads with ST-segment depression, the duration of ST-segment depression, the heart rate at the onset of ST-segment depression, and the exercise duration before ST-segment depression were recorded. 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.06.001
703
TABLE 1 Characteristics of the Study Patients Magnitude of Ischemia Characteristic Men Age (yrs) Body mass index (kg/m2) Chest pain Typical chest pain Dyslipidemia Hypertension Diabetes mellitus Tobacco use Percutaneous coronary revascularization Myocardial infarction Surgical coronary revascularization Medication usage Aspirin  Antagonist Statin ACE inhibitor Diuretic Calcium-2⫹ receptor antagonist Dihydropyridine class Long-acting nitrate
Total (n ⫽ 1,006)
None (n ⫽ 701)
Mild (n ⫽ 109)
Moderate (n ⫽ 135)
Severe (n ⫽ 61)
p Value*
613 (60.9%) 59 ⫾ 11 28.3 ⫾ 5.5 532 (52.9%) 357 (35.5%) 624 (62.0%) 610 (60.6%) 171 (17.0%) 123 (12.2%) 279 (27.7%) 196 (19.5%) 142 (14.1%)
370 (53%) 58 ⫾ 12 28.2 ⫾ 5.3 365 (52%) 235 (34%) 395 (56%) 412 (59%) 102 (15%) 84 (12%) 150 (21%) 93 (13%) 65 (9%)
81 (74%) 61 ⫾ 12 28.2 ⫾ 5.0 56 (51%) 29 (27%) 81 (74%) 74 (68%) 22 (20%) 15 (14%) 43 (39%) 45 (41%) 31 (28%)
114 (84%) 62 ⫾ 10 28.3 ⫾ 5.8 71 (52%) 60 (44%) 103 (76%) 80 (59%) 32 (24%) 19 (14%) 62 (46%) 44 (33%) 36 (27%)
48 (79%) 60 ⫾ 10 30.0 ⫾ 6.7 41 (67%) 33 (54%) 45 (75%) 44 (72%) 15 (25%) 5 (8%) 24 (39%) 14 (23%) 10 (16%)
⬍0.001 0.009 0.098 0.145 ⬍0.001 ⬍0.001 0.075 0.014 0.653 ⬍0.001 ⬍0.001 ⬍0.001
574 561 554 362 160 106 62 75
372 343 341 227 119 77 43 38
(57.1%) (55.8%) (55.1%) (36.0%) (15.9%) (10.5%) (6.2%) (7.5%)
(53%) (49%) (49%) (32%) (17%) (11%) (6%) (5%)
73 73 73 48 14 8 4 9
(67%) (67%) (67%) (44%) (13%) (8%) (4%) (8%)
93 98 96 62 21 16 12 16
(69%) (73%) (71%) (46%) (16%) (12%) (9%) (12%)
36 47 44 25 6 4 3 12
(59%) (77%) (72%) (41%) (10%) (7%) (5%) (20%)
⬍0.001 ⬍0.001 ⬍0.001 0.004 0.383 0.568 0.381 ⬍0.001
*The p value is reported for the association with increasing magnitude of ischemia. ACE ⫽ angiotensin-converting enzyme.
Protocol for myocardial perfusion imaging: Patients were injected with 8 to 13 mCi technetium-99m sestamibi (Cardiolite, Bristol-Myers Squibb Imaging Inc., North Billerica, Massachusetts) at rest, and gated SPECT imaging was initiated 15 to 30 minutes later with a 3-detector (Prism 3000, Picker International Inc., Bedford Heights, Ohio) or 2-detector (e.cam duet, Siemens Medical Solutions, Hoffman Estates, Illinois) gamma camera. During maximal exercise, patients were injected with 25 to 35 mCi technetium-99m sestamibi and then exercised for an additional 60 seconds. Gated SPECT imaging was initiated 15 to 30 minutes later on the same gamma camera. Images were transferred to a dedicated workstation and analyzed by using standard, commercially available software (e.soft, Siemens Medical Solutions). Tomographic images were reconstructed by using filtered backprojection with a Butterworth filter (power 5, cut-off frequency 0.79 cycles/pixel). Gated images were reconstructed in the same manner with 8 frames per cardiac cycle. One nuclear cardiologist (SD or MFDC) reviewed each myocardial perfusion image. A 17-segment, 5-point (0 ⫽ normal uptake, 4 ⫽ absent uptake) scoring system was used to compute a summed stress score, summed rest score, and summed difference score. In patients with abnormal images (summed stress score ⬎3), the magnitude of ischemia was classified as none (summed difference score 0), mild (1 to 3), moderate (4 to 7), or severe (ⱖ8). The magnitude of fixed defects was classified as none (summed difference score 0), mild (1 to 3), moderate (4 to 7), or severe (ⱖ8). Each segment was assigned to a coronary arterial territory based on a generally accepted standard.16 Statistical analysis: Numerical data are presented as mean ⫾ SD. Data for the summed data score were skewed and are reported as the mean, median, and 704 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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interquartile range (25th to 75th percentile). Categorical and ordinal data are presented as counts and percentages, respectively. The relation of clinical characteristics and ETT parameters to the results of myocardial perfusion imaging were analyzed with the chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests. Analysis of the relation of ST-segment depression to the location of ischemia was restricted to those patients with ischemia limited to a single vascular territory. Adjustment of the relation between ST-segment depression and the severity of ischemia was performed with ordinal logistic regression, including all variables with a univariate p value ⬍0.2. The relations between different parameters of ST-segment depression were evaluated with Spearman’s correlation. Statistical analysis was performed with SAS 8.2 for Windows (SAS Institute, Cary, North Carolina).
RESULTS
Characteristics of the study cohort: A total of 1,006 patients was included in the study cohort. Clinical characteristics and ETT parameters of the study cohort are shown in Tables 1 and 2, respectively. Quantitative relation of ST-segment depression to the magnitude of ischemia on myocardial perfusion imaging:
ST-segment depression was present in 232 patients (23%), and ischemia was present in 305 patients (30%). ST-segment depression was present without ischemia in 107 patients (11%), and ischemia was present without ST-segment depression in 180 patients (18%). The presence of ST-segment depression was strongly associated with an increasing magnitude of ischemia (p ⬍0.001; Table 2). After adjustment for potential confounders, the association remained highly significant (p ⬍0.001). There was no significant association between the presSEPTEMBER 15, 2004
TABLE 2 Exercise Treadmill Test Parameters Magnitude of Ischemia Parameter Baseline electrocardiogram Nonspecific T-wave changes Right bundle branch block Left atrial abnormality Previous myocardial infarction Anterior Inferior Lateral Exercise Heart rate at rest (beats/min) Systolic blood pressure at rest (mm Hg) Diastolic blood pressure at rest (mm Hg) Peak heart rate (beats/min) Peak systolic blood pressure (mm Hg) Exercise duration (min) Symptoms Chest pain Dyspnea Reason for termination Fatigue Chest pain Hypertensive response Marked STD Hypotension Other STD (ⱖ1 mm) Maximal heart rate without STD (beats/min) Maximal exercise duration without STD (min)
Total (n ⫽ 1,006)
None (n ⫽ 701)
Mild (n ⫽ 109)
278 72 29 95 54 49 13
(28%) (7%) (3%) (9%) (5%) (5%) (1%)
175 (25%) 45 (6%) 21 (2%) 35 (5%) 24 (3%) 13 (2%) 3 (⬍1%)
41 9 2 31 14 18 5
66 129 78 138 186 8.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
67 129 79 141 188 8.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
65 128 78 135 182 7.8
24 17 9 22 24 2.9
27 16 9 22 23 2.9
(38%) (8%) (2%) (28%) (13%) (17%) (5%) ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
12 17 8 23 29 3.0
195 (19%) 230 (23%)
102 (15%) 151 (15%)
22 (20%) 29 (27%)
849 (84%) 66 (7%) 33 (3%) 25 (3%) 11 (1%) 52 (5%) 232 (23%) 135 ⫾ 23 7.4 ⫾ 3.1
609 (87%) 32 (5%) 29 (4%) 8 (1%) 4 (1%) 35 (5%) 107 (15%) 139 ⫾ 23 7.7 ⫾ 3.0
85 (87%) 4 (4%) 2 (2%) 2 (2%) 1 (1%) 5 (5%) 26 (24%) 131 ⫾ 24 7.3 ⫾ 3.2
Moderate (n ⫽ 135) 45 13 5 24 13 13 5 64 127 77 130 181 7.9
(33%) (10%) (4%) (18%) (10%) (10%) (4%) ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
11 20 9 20 25 2.9
43 (32%) 38 (28%) 108 (80%) 16 (12%) 1 (1%) 7 (5%) 4 (3%) 9 (7%) 57 (42%) 124 ⫾ 20 6.8 ⫾ 2.9
Severe (n ⫽ 61) 17 5 1 5 3 2
68 135 81 132 182 7.6
p Value*
(28%) (8%) (2%) (8%) (5%) (3%) 0
0.018 0.549 0.772 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
0.639 0.017 0.005 ⬍0.001 0.006 0.556
13 19 8 17 29 3.1
28 (46%) 12 (20%)
⬍0.001 0.256
37 (61%) 14 (23%) 1 (2%) 8 (13%) 2 (3%) 3 (5%) 42 (69%) 124 ⫾ 20 5.9 ⫾ 3.1
⬍0.001 ⬍0.001 0.133 ⬍0.001 0.031 0.863 ⬍0.001 ⬍0.001 ⬍0.001
*The p value is reported for the association with increasing magnitude of ischemia. STD ⫽ ST-segment depression.
ence of ST-segment depression and the magnitude of fixed defects (p ⫽ 0.543). The relation between ST-segment depression and the magnitude of ischemia was further evaluated by stratifying the magnitude, extent, and duration of STsegment depression (Figure 1). Increasing magnitudes of ischemia were associated with more frequent, more severe, more extensive, and more prolonged ST-segment depression (p ⬍0.001 for all). Conversely, increased magnitude, extent, and duration of ST-segment depression were associated with increased ischemia (p ⬍0.001 for all; Table 3). The magnitude, extent, and duration of ST-segment depression were highly correlated with each other (r ⬎0.99, p ⬍0.001 for all) and displayed similar relations to the magnitude of ischemia. There was no statistically significant association of any measure of ST-segment depression with fixed defects (Table 3). Adjusted odds ratios were calculated for the association of ST-segment depression with increasing magnitude of ischemia. At each break point on the ischemia scale, the odds ratio represents the probability of a patient belonging to the group with greater ischemia as opposed to the probability of belonging to the group with less ischemia. The magnitude, extent, and duration of STsegment depression were strongly associated with increasing ischemia at each break point on the ischemia scale (p ⬍0.001; Figure 2). The association was greatest with severe ischemia (summed difference score ⱖ8) and
for ST-segment depression ⱖ2 mm, in ⱖ6 leads, or for ⱖ7 minutes. Of all variables measured, the magnitude, extent, and duration of ST-segment depression showed the strongest relation to the magnitude of ischemia. The maximal value of R2 for any of the models was ⬍0.35.
Relation of the magnitude of ST-segment depression to the location of ischemia: Of the 305 patients in the
study cohort with ischemia, 153 (50%) had ischemia confined to a single coronary arterial territory, 118 (39%) had ischemia in 2 coronary arterial territories, and 34 (11%) had ischemia in all 3 coronary arterial territories. The magnitude of ST-segment depression increased progressively with the number of coronary arterial territories involved (p ⫽ 0.007; Figure 3). Of those with ischemia in a single coronary arterial territory, 51 (33%) had ischemia in the usual left anterior descending coronary artery territory, 32 (21%) had ischemia in the usual left circumflex coronary artery territory, and 70 (46%) had ischemia in the usual right coronary artery territory. There was no significant association of the location of ischemia and the magnitude of ST-segment depression (p ⬎0.10; Figure 4). Data for the extent and duration of ST-segment depression were similar.
DISCUSSION We found a strong and highly statistically significant positive association between ST-segment depression during ETT and the global magnitude of ischemia
CORONARY ARTERY DISEASE/MECHANISM OF ST-SEGMENT DEPRESSION
705
FIGURE 1. The prevalence, magnitude (A), extent (B), and duration (C) of ST-segment depression (STD) increases with increasing magnitude of ischemia, and the proportion of patients with no STD decreases as the magnitude of ischemia increases (p <0.001 for all).
as assessed by technetium-99m SPECT myocardial perfusion imaging. The magnitude, extent, and duration of ST-segment depression were highly correlated with each other and had similar relations to the magnitude of ischemia. After adjustment for all significant clinical and ETT parameters, these relations remained strongly significant. The presence of ST-segment depression ⱖ1 mm during ETT is commonly used for the diagnosis of CAD and predicts the occurrence of adverse events associated with CAD.2 The mechanism for the development of ST-segment depression during ETT is incompletely understood but is believed to be an electrical manifestation of underlying myocardial 706 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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ischemia. The presence and number of reversible perfusion defects found during myocardial perfusion imaging are also valuable for the diagnosis of CAD.1 ETT is often performed contemporaneously with myocardial perfusion imaging, and the results of the tests are usually concordant but discordant often enough to question the true relation of ST-segment depression to ischemia.3–5 Several previous studies have investigated this relation with different results.6 –10 Three smaller studies using thallium-201 myocardial perfusion imaging, 2 using planar imaging,7,8 and 1 using SPECT imaging11 found an insignificant or no relation of the magnitude of ST-segment depression to the magnitude of ischemia, even in patients with profound ST-segment depression.7 One study using technetium-99m SPECT myocardial perfusion imaging associated larger perfusion defects with an increased magnitude of ST-segment depression only among patients who had STsegment depression during ETT, thus excluding those with ischemia but no ST-segment depression,6 whereas another found that the magnitude of STsegment depression was not a good predictor of ischemia.10 We evaluated a large cohort of patients who underwent contemporaneous ETT and technetium-99m myocardial perfusion imaging and found that there was a highly statistically significant increase in the magnitude of ischemia in patients with ST-segment depression (Table 3). Moreover, the prevalence and magnitude of ST-segment depression increased uniformly with the magnitude of ischemia (p ⬍0.001; Figure 1). The previous negative studies were likely underpowered due to small sample sizes, but an additional factor may have been the improved imaging characteristics of technetium-99m versus those of thallium-201. The relation between ischemia and the extent and duration of ST-segment depression has been little studied. One study found that the extent of ST-segment depression was significantly associated with ischemia,6 whereas another found no relation between ischemia and the duration of ST-segment depression. We found that the extent and duration of ST-segment depression were highly correlated with each other (r ⬎0.99, p ⬍0.001 for all) and had similar, strong relations to the magnitude of ischemia (p ⬍0.001 for all; Figure 1 and Table 3). After adjustment for all potential confounders, the relation between ischemia and the magnitude, extent, and duration of ST-segment depression remained similar and highly statistically significant (p ⬍0.001 for all; Figure 2) and demonstrated the strongest relation of any of the variables tested. These results and the high correlation of the magnitude, extent, and duration of ST-segment depression with each other strongly suggest that these measures of ST-segment depression reflect a common underlying phenomenon that is ischemia or the result of ischemia. However, the relatively modest R2 value suggests that other significant causative factors remain to be elucidated. An alternative relation between ST-segment deSEPTEMBER 15, 2004
TABLE 3 Relation Between Indexes of ST-Segment Depression and Summed Difference Score Summed Difference Score Variable
n (%)
Mean
Median
IQR
No ST-segment depression ST-segment depression ⬍2 mm ⱖ2 mm In ⬍6 leads In ⱖ6 leads ⬍7 min ⱖ7 min
774 (77%)
1.0
0
0–0
130 102 84 147 120 112
2.3 5.1 2.7 4.0 2.6 4.5
0 4 0 3 0 4
0–4 0–8 0–4 0–7 0–4 0–7
(13%) (10%) (8%) (15%) (12%) (11%)
Summed Rest Score p Value
⬍0.001 ⬍0.001 ⬍0.001
Mean
Median
IQR
2.6
1
0–3
1.9 3.1 2.5 2.4 1.8 3.0
1 2 1 1 1 1
0–2 0–4 0–4 0–4 0–2 0–4
p Value
0.060 0.472 0.156
IQR ⫽ interquartile range.
FIGURE 3. The relation between the magnitude of ST-segment depression (STD) and the number of coronary arterial territories with ischemia. The magnitude of STD progressively increases as the number of coronary arterial territories with ischemia increases (p ⴝ 0.007).
FIGURE 2. Adjusted odds ratios for the association of the magnitude, extent, and duration of STD with ischemia. Each data point represents the odds ratio for having increased ischemia versus with less ischemia at each break point in the ischemia magnitude scale. None (N) 3 mild (m) moderate (M) severe (S) ⴝ odds ratio for having mild, moderate, or severe ischemia versus no ischemia; N m 3 M S ⴝ odds ratio for having moderate or severe ischemia versus no or mild ischemia; N m M 3 S ⴝ odds ratio for having severe ischemia versus no, mild, or moderate ischemia. Adjusted odds ratios account for all significant clinical and ETT parameters. Other abbreviation as in Figure 1.
pression and ischemia has been proposed in which the magnitude of ST-segment depression decreases with increasing ischemia because the electrical forces from ischemia in opposing walls negate each other and result in less ST-segment depression than does ischemia in a single territory.12–14 Previous investigations have shown an increased prevalence of ST-segment depression with increased severity of CAD.2 We found that increasing prevalence, magnitude, extent, and duration of ST-segment depression were positively associated with the number of coronary arterial territories involved (Figure 3), suggesting that the association between ST-segment depression and the magnitude of ischemia is not affected by cancellation of electrical forces.
Several previous studies have shown that there is little relation between the location of ischemia and the presence and magnitude of ST-segment depression during ETT.6,17–19 The results of our investigation are consistent with these findings. Given the large number of patients in our study cohort, there were large numbers of clinical and ETT parameters that were associated with increasing ischemia (Tables 1 and 2). Evidence of previous CAD, established risk factors for CAD, medication use for the treatment of CAD, and evidence of a positive ETT had the most consistent associations with the magnitude of ischemia. The ability to exercise to the point of fatigue without other symptoms or achieve a high rate–pressure product was protective. We did not use invasive coronary angiography to determine the extent of CAD. Although invasive coronary angiography is superior for the diagnosis of CAD, the semiquantitative method that we used to determine the magnitude of ischemia is commonly used, straightforward to determine, and provides more direct information about myocardial ischemia than about epicardial coronary disease that, in the presence of previous infarction, may not necessarily result in ischemia. We limited our study population to those patients who were able to exercise and had a diagnos-
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5. Vanzetto G, Ormezzano O, Fagret D, Comet M, Denis B, Machecourt J.
FIGURE 4. Relation of the magnitude of STD to the location of ischemia. Among patients with ischemia confined to a single coronary arterial territory, the association between the magnitude of STD and the location of ischemia was not significant (p >0.1). LAD ⴝ left anterior descending coronary artery, LCx ⴝ left circumflex coronary artery, RCA ⴝ right coronary artery. Other abbreviation as in Figure 1.
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