In patients with obstructive coronary artery disease, electrocardiographic (ECG) ST-segment elevation (STE) is frequently seen during dobutamine stress echocardiography (DSE) in leads overlying previous transmural left ventricular (LV) myocardial infarction. The mechanism of occasional STE during DSE in LV region with inducible myocardial ischemia and no previous myocardial infarction has not been well delineated. We retrospectively identified 28 adults (age 51 to 83 years [69 ± 8]; 82% men) with STE (>1 mm at ≥80 ms after J point in ≥2 contiguous leads without pathologic Q waves) and inducible myocardial ischemia in the same territory during DSE. STE occurred in inferior (n = 16), inferolateral (n = 8), anterior (n = 1), lateral (n = 2), or anterolateral (n = 1) leads and was associated with ischemic symptoms in 17 patients (61%). Inducible LV wall motion abnormality developed in LV segments corresponding to ECG STE in all patients. Coronary arteriography (within 1 week of the index DSE) showed severe luminal narrowing in the major epicardial coronary artery supplying the region with DSE STE and ischemia (90% to 99% in 9 patients [32%] and 100% in 19 patients [68%]). The ischemic region was supplied by ipsilateral (n = 4 [14%]), contralateral (n = 21 [75%]), or both ipsilateral and contralateral (n = 3 [11%]) collateral branches. In conclusion, dobutamine-induced ECG STE in LV segments with normal baseline wall motion is a highly reliable marker of viable collateral-dependent myocardium.
Dobutamine stress echocardiography (DSE) is an established alternative to exercise stress testing for detection of coronary artery disease (CAD). Continuous electrocardiographic (ECG) monitoring and frequent 12-lead ECG tracings are obtained during DSE and are primarily used to detect potentially life-threatening arrhythmias. Unlike exercise stress echocardiography, limited concordance exists between inducible wall motion abnormality (WMA) and “ischemic” ECG changes during DSE. Previous studies have reported ST-segment elevation (STE) during DSE in high proportion of patients with previous Q-wave myocardial infarction and have attributed the finding to augmented dyssynergy of or residual viability in the infarct region. In the absence of previous infarct, STE and inducible myocardial ischemia have been reported in patients with dobutamine-induced coronary artery spasm or regional left ventricular (LV) ballooning. Some studies have shown that STE and inducible WMA during DSE may also occur in patients with obstructive CAD by angiography. The aim of this study was to delineate the relation of dobutamine-induced STE (in the absence of pathologic Q waves over LV regions with normal systolic thickening at baseline) to angiographic severity of CAD and presence of collateral circulation.
Methods
The study subjects were identified among all DSE studies performed from January 2000 to August 2010 at the Geisinger Medical Center. Patients were included if they fulfilled the following criteria: a standard dobutamine-atropine study was performed for assessment of symptoms suggestive of obstructive CAD, all 12-lead ECG tracings obtained during DSE were available for review, and an STE of ≥1 mm was noted during DSE at 80 ms after the J point in ≥2 contiguous leads without baseline STE or pathologic Q waves and was associated with new (ischemic) WMA in LV regions represented by the ECG leads with STE. Patients were excluded if baseline LV WMA was present in regions represented by the ECG leads with dobutamine-induced STE, significant conduction disease (QRS duration of ≥120 ms) was present, coronary arteriography was not performed within a week after the index DSE, and DSE images and coronary angiographic images were not available for review.
All DSE studies were performed according to a standard dobutamine-atropine protocol and included complete Doppler echocardiography at rest. Incremental doses of dobutamine (5 to 50 mg/kg/min) were infused at 3-minute intervals. If the target (≥85% of age-predicted maximum) heart rate was not reached and in the absence of inducible ischemia, atropine was injected intravenously at 0.25 to 0.5 mg doses up to a maximum dose of 2 mg. Echocardiographic images were obtained in the standardized parasternal long- and short-axes (basal, midventricular, and apical) and apical (2-, 3-, 4-, and 5-chamber) views at each stage and were stored digitally. During dobutamine infusion, a 12-lead electrocardiogram was recorded and blood pressure was measured at each stage. Inducible myocardial ischemia, defined as normal regional wall motion at baseline followed by development of WMA in ≥2 contiguous LV segments at the final stage of the test and return to normal during recovery, occurred in all patients. This was associated with transient STE in ECG leads corresponding to the ischemic LV region.
Digitally stored echocardiographic images were analyzed off-line by viewing synchronized corresponding cineloops obtained at baseline, low-dose, prepeak (∼70% predicted maximum heart rate for age), peak (onset of myocardial ischemia), and recovery stages in quad-screen format. For wall motion assessment, a 16-segment model of LV was adopted and wall motion was scored on a 4-point scale as 1 = normal or hyperkinetic, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic or aneurismal. This was objectively determined by assessment of systolic wall thickening relative to diastolic wall thickness in each of the 16 segments as normal (≥1.3), hypokinetic (1.1 to 1.29), akinetic (<1.1), and dyskinetic (<1.1 with systolic paradoxical outward motion). Segmental response to dobutamine was defined as normal, ischemic, or abnormal (viable or nonviable segments with resting asynergy). LV ejection fraction was measured at baseline using the biplane disc summation method.
Significant coronary stenosis was defined by selective coronary artery angiography as >70% luminal narrowing in a major epicardial artery or its main branches. Coronary collateral circulation was graded as 0 = no collaterals, 1 = side branch filling of the recipient artery without filling of the main epicardial artery, 2 = partial filling of the main epicardial recipient artery, and 3 = complete filling of the main epicardial recipient artery. The study protocol was reviewed and approved by the Geisinger Medical Center Institutional Research Review Board.
Data are expressed as mean ± SD for continuous variables and as frequencies and percentages for categorical variables. A p value <0.05 was considered statistically significant. All statistical analyses were performed on SPSS software for Windows (version 18.0, SPSS Inc, Chicago, Illinois).
Results
The 28 adults ranged in age from 51 to 83 years (mean 69 ± 8) and 23 (82%) were men. The remaining characteristics of these patients are listed in Table 1 . A history of CAD was present in 14 patients (50%), and 6 (21%) had remote myocardial infarction. Previous coronary interventions (remote) were performed in 13 (46%).
| Variable | Value (%) |
|---|---|
| Age (yrs) | 51–83 (69 ± 8) |
| Men | 23 (82) |
| Hypertension ∗ | 26 (93) |
| Diabetes mellitus | 15 (54) |
| Hyperlipidemia † | 22 (79) |
| Smoker | 16 (57) |
| Family history of CAD | 14 (50) |
| Body mass index (kg/m 2 ) | 22–47 (32 ± 6) |
| >30 | 17 (60) |
| Previous percutaneous coronary intervention | 5 (18) |
| Previous coronary artery bypass surgery | 8 (29) |
| Previous myocardial infarction | 6 (21) |
| Anterior | 1 (4) |
| Inferior | 5 (18) |
| Heart failure | 2 (7) |
| Medications | |
| Aspirin | 21 (75) |
| Cholesterol-lowering agent | 16 (57) |
| β-adrenergic blocking agent | 14 (50) |
| Angiotensin-converting enzyme inhibitor | 17 (61) |
∗ Blood pressure of >140/90 mm Hg or on pharmacologic therapy for known hypertension.
† Total cholesterol of >200 mg/dl or on pharmacologic therapy for known hyperlipidemia.
Baseline LV WMA was present in 9 patients (32%) including 7 with inferior and 2 with anterior wall myocardial infarction and included a total of 45 asynergic segments (10%) of the 448 segments examined. The 45 asynergic segments consisted of 23 hypokinetic (51%), 20 akinetic (44%), and 2 dyskinetic (5%) segments. The asynergic segments involved the basal LV in 16 (36%), mid-LV in 16 (36%), and apical LV in 13 (28%) segments. None of these baseline LV WMAs were in the regions with dobutamine-induced STE. Baseline LV segmental wall motion score ranged from 1 to 1.75 (mean 1.15 ± 0.23) among the 28 patients. The LV ejection fraction ranged from 32% to 67% (mean 54 ± 15%) and was <55% in 7 patients (25%).
Dobutamine was infused at a peak rate of 20 to 50 μg/kg/min (mean 38 ± 9), and atropine was given to 16 patients (57%) in cumulative doses of 0.25 to 2 mg (mean 0.8 ± 0.5). New ECG STE of 1 to 3 mm occurred at peak dobutamine infusion and involved the inferior (16 [57%]), inferolateral (8 [29%]), anterior precordial (1 [3.5%]), lateral (2 [7%]), and anterolateral (1 [3.5%]) leads ( Table 2 ). This was associated with symptoms of angina (14 [50%]), dyspnea (1 [3.5%]), or throat tightness (3 [11%]) in 17 patients (61%). New segmental LV WMA developed in all patients at peak stress and involved the inferior (with or without basal inferoseptal; 14 [50%]), inferior and inferolateral (7 [25%]), anterior and anteroseptal (4 [14%]), inferolateral (2 [7%]), and anterolateral (1 [4%]) regions. Ischemia occurred at a range of percent maximum heart rate for age of 73% to 97% (mean 86 ± 6%). Overall, 20 patients (71%) reached target heart rate (≥85% of age-predicted maximum).
| Variable | Value, n (%) |
|---|---|
| Baseline echocardiographic LV WMA | 9 (32) |
| ECG STE | |
| Inferior (II, III, aVF) | 16 (57) |
| Inferolateral (II, III, aVF, V 5 , V 6 ) | 8 (29) |
| Anterior precordial (V 1 –V 4 ) | 1 (3.5) |
| Lateral (I, aVL, V 5 , V 6 ) | 2 (7) |
| Anterolateral (V 2 –V 6 , I, aVL) | 1 (3.5) |
| New LV WMA | 28 (100) |
| Inferior | 10 (36) |
| Inferoposterior | 7 (25) |
| Inferior + basal inferoseptal | 4 (14) |
| Anterolateral | 1 (3.5) |
| Anterior | 4 (14) |
| Inferolateral | 2 (7) |
In all 28 patients, the coronary artery supplying the LV regions with inducible ischemia on DSE showed high-grade stenosis in its proximal segment including 9 (32%) with 90% to 99% (95 ± 4%) stenoses and 19 (68%) with chronic total occlusion. The culprit artery, responsible for inducible myocardial ischemia during DSE, was right (22 [79%]), left circumflex (4 [14%]), or left anterior descending (2 [7%]) coronary arteries. In 23 patients (82%), the culprit vessel was a native coronary artery, whereas in 5 (18%), it was a saphenous vein graft either to the right (n = 4) or to the left circumflex (n = 1) coronary artery. Visible collateral arteries (grades 2 or 3) from ipsilateral (4 [14%]), contralateral (21 [75%]), or both (3 [11%]) supplied the distal segment of the culprit vessel. The collateral circulation was graded as 2 in 6 (21%) and 3 in 22 patients (79%). None of the coronary arteries supplying contralateral collaterals to the ischemia-related artery showed significant stenosis.
Discussion
The data presented provide evidence for a direct relation between a specific coronary artery anatomy (chronic total or near total obstruction with distal vessel filling by collateral vessels) and development of myocardial ischemia and STE during DSE. Dobutamine-induced STE has been reported as part of other clinical scenarios including patients with “severe obstructive CAD” ( Table 3 ). The current data suggest that STE during DSE in such patients can be a marker of collateral-dependent myocardium.
