The prognostic value of ST-segment depression on exercise electrocardiogram (eECG) in the setting of a normal wall motion response in a stress echocardiographic study is not well defined. The aim of the study was to compare outcomes among patients with normal wall motion during stress echocardiography with and without ischemic exercise electrocardiographic changes. A total of 4,233 patients underwent stress echocardiography from 2007 to 2010. The primary outcomes were a composite of all-cause mortality and myocardial infarction. Coronary revascularization was a secondary outcome. A Cox regression model was used for the primary analysis. Ischemic exercise electrocardiographic changes were defined as ST-segment depression of at least 1 mm, on at least 3 consecutive beats, and in at least 2 contiguous leads. A normal stress echocardiogram was present in 2,975 patients; of them, 2,228 (74%) had a normal eECG and 747 (26%) had ischemic changes on eECG. Patients with and without ischemic changes during exercise electrocardiography were similar in age and gender. At 4-years follow-up, 36 patients (2.8%) with a normal eECG experienced a primary end point versus 12 patients (1.9%) in the group with an ischemic exercise electrocardiographic response (p = 0.56). The rate of coronary revascularization was similar between the groups (7.0% and 5.7%, respectively, p = 0.2). There were no differences in the primary outcomes of patients with and without exercise electrocardiographic changes and normal stress echocardiogram (hazard ratio 1.33, 95% confidence interval 0.69 to 2.58). In conclusion, a normal wall motion response even in the setting of an ischemic exercise electrocardiographic response portends a benign prognosis in patients undergoing stress echocardiography.
Although the prognostic value of exercise electrocardiography and stress echocardiography are well established, there is little information available about whether patients who have ischemic changes on the exercise electrocardiogram (eECG) but normal wall motion contractility during stress echocardiography have a worse prognosis than those patients with a normal eECG and wall motion response. The objectives of the present study of a large cohort of patients undergoing stress echocardiography was to assess the rates of the composite outcome of all-cause mortality and myocardial infarction (MI) and coronary revascularization between patients with and without ischemic eECG during a normal stress echocardiography in reference to the group with abnormal stress echocardiogram.
Methods
We studied 4,233 consecutive patients who underwent stress echocardiography from January 2007 through December 2010. Patients with nonspecific ST-segment changes on the eECG (n = 588, 14%), inconclusive results on the stress echocardiogram because of poor echocardiographic imaging (n = 331, 8%), or who were lost to follow-up (n = 22, 0.5%) were excluded. Thus 3,322 patients were monitored for a median of 27 months. This study was approved by the local committee for human research.
All stress echocardiographic testing was performed on a treadmill using the Bruce protocol. Echocardiographic images were obtained from standard views, at rest and within 30 seconds of termination of exercise. The left ventricle (LV) was divided into 16 segments and its contractility evaluated in accordance with guidelines established by the American Society of Echocardiography. LV ejection fraction was visually estimated. A study was considered inconclusive when ≥2 LV segments were not clearly visualized by echocardiography. In those cases in which the segmental LV contractility was unclear, a second cardiologist examined the study; the wall motion assessment was determined by a consensus between the readers.
Exercise was terminated when patients achieved the target heart rate defined as ≥85% maximal predicted rate or if the patient experienced angina, dyspnea, significant arrhythmia, or fatigue. A standard 12-lead electrocardiogram was obtained at rest for all the patients and monitored throughout both the exercise and recovery phases. The eECG was considered ischemic if ≥1 mm ST-segment depression was present after 0.08 seconds after the J point and was present in at least 3 consecutive beats in at least 2 contiguous leads during peak stress. Any change in the ST segment on exercise in patients with left bundle branch block, preexcitation syndrome, LV strain, or significant ST changes on baseline electrocardiogram was considered as nonspecific for ischemia.
Three groups of patients were identified: normal stress echocardiogram and normal eECG (group I); normal stress echocardiogram but ischemic change present on eECG (group II), and abnormal stress echocardiogram defined as worsening of LV contractility by at least 1 grade in at least 1 segment immediately after exercise compared with rest and regardless of the exercise electrocardiographic result (group III).
Primary outcomes were defined as a composite of all-cause mortality and MI. Secondary outcomes included coronary revascularization defined as percutaneous coronary intervention or coronary artery bypass graft surgery. In the primary analysis, we compared groups with and without ischemic exercise electrocardiographic changes and normal stress echocardiogram and those with abnormal stress echocardiogram (reference group). In the secondary analysis, we compared patients with and without ST-segment depression ≥2 mm on eECG and normal stress echocardiogram.
Data were summarized using frequency tables for categorical variables and summary statistics (mean with SD) for continuous variables. T tests and analysis of variance were used to compare continuous variables, and Pearson’s chi-square test for categorical variables. Not-normally distributed variables were presented as median and interquartile range. Survival free of MI and death or free of percutaneous coronary intervention or coronary artery bypass graft in groups that underwent stress echocardiography was estimated using the Kaplan-Meier (KM) method and compared by the log-rank test. KM estimates of the outcomes were calculated for 1 and 4 years of follow-up. Multivariate analysis was performed using Cox proportional hazards regression method to assess the impact of the result of stress examination, gender, age, and co-morbidities on the incidence of the primary outcome. Proportionality of hazards was assessed by evaluating the interaction between time to event and group. All reported p values are 2-sided and the level of p <0.05 was considered statistically significant. Data analysis was performed using SPSS, version 18 (SPSS Inc., Chicago, Illinois).
Results
Of the 3,322 patients studied, 2,975 had a normal stress echocardiogram; of these, 2,228 (74%) had a normal eECG (group I) and 747 (26%) had ischemic changes on the eECG (group II). There were 347 patients with exercise-induced LV wall motion abnormalities (group III). Baseline characteristics for the 3 groups are listed in Table 1 .
| Variable | Negative Echo Negative Stress ECG (Group I; n = 2,228) | Negative Echo Positive Stress ECG (Group II; n = 747) | Positive Echo Positive ECG (n = 219 [63%]) Negative ECG (n = 128 [37%]) Group III, n = 347 | p Value |
|---|---|---|---|---|
| Age (yrs) | 57.4 ± 18.2 | 56.7 ± 10.9 | 66.8 ± 9.8 | <0.001 |
| Women | 881 (40) | 316 (42) | 102 (29) | <0.001 |
| Diabetes mellitus | 190 (9) | 51 (7) | 44 (13) | 0.006 |
| Dyslipidemia (total cholesterol ≥240 mg/dl) | 551 (25) | 147 (20) | 118 (34) | <0.001 |
| Hypertension | 441 (20) | 112 (15) | 98 (28) | <0.001 |
| Previous MI | 58 (2.6) | 5 (0.5) | 17 (4.9) | <0.001 |
| Chronic ischemic heart disease | 353 (16) | 81 (11) | 100 (29) | <0.001 |
| Chest pain as reason for stress echocardiography | 928 (42) | 259 (35) | 101 (29) | <0.001 |
| Workload (METs) | 8.6 ± 2.8 | 9.5 ± 2.7 | 9.1 ± 2.0 | 0.003 |
| Maximal predictive heart rate (%) | 92 ± 5 | 91 ± 5 | 86 ± 4 | 0.707 |
| Exercise duration (min) | 9.9 ± 2.1 | 10.7 ± 2.8 | 9.6 ± 2.3 | 0.004 |
| Rest wall motion score index | 1.11 ± 0.13 | 1.02 ± 0.11 | 1.91 ± 0.24 | <0.001 |
| Stress wall motion score index | 1.09 ± 0.16 | 1.01 ± 0.10 | 2.33 ± 0.34 | <0.001 |
| LV ejection fraction | ||||
| ≥55% | 2,147 (96) | 742 (99) | 261 (75) | <0.001 |
| ≥45% and <55% | 49 (2.4) | 4 (0.6) | 52 (15) | |
| ≥35% and <45% | 25 (1.3) | 1 (0.1) | 25 (7.2) | |
| <35% | 6 (0.3) | 0 (0) | 8 (2.3) |
Figure 1 depicts the KM survival curves for the primary end point analysis. During the follow-up period, 36 of 2,228 patients in group I and 12 of 747 patients in group II experienced a primary outcome event, namely, MI or all-cause mortality (4-year KM rates of 2.8% vs 1.9%, log-rank p = 0.56). Four-year MI rates (group I with 22 of 2,228, KM rate of 1.6% vs group II with 8 of 747, KM rate of 1.3%, log-rank p = 0.49) and death (group I with 22 of 2,228, KM rate of 1.1% vs group II with 8 of 747, KM rate of 0.5%, log-rank p = 0.94) were similar between the groups. Of the 126 patients who had ≥2 mm of ST-segment depression on eECG and a normal stress echocardiogram, only 1 patient in this group experienced a primary outcome (MI) during the 4 years of follow-up, and 9 of these 126 patients had ≥3-mm ST-segment depression on their eECG. None of these patients died or had an MI.
Patients with an abnormal stress echocardiogram had a 4-year rate of revascularization of 35%. Figure 2 depicts the comparison of time with revascularization among patients with a normal stress echocardiogram. The 4-year rate of revascularization was similar between patients with normal eECG and with abnormal eECG (7.0% vs 6.7%, log-rank p = 0.2). In patients with an ischemic eECG, the incidence of revascularization did not differ between the patients with ≥2 mm of ST depression and <2 mm ST-segment depression: 4-year rates 8.3% and 10.3%, respectively, log-rank p = 0.36.
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