Safety and Accuracy of Dobutamine-Atropine Stress Echocardiography for the Detection of Residual Stenosis of the Infarct-Related Artery and Multivessel Disease During the First Week After Acute Myocardial Infarction
Background The safety of dobutamine-atropine echocardiography early after acute myocardial infarction is unknown. Its accuracy for the early detection of infarct artery stenosis and multivessel coronary artery disease is also unclear. The objective of the present study was to document its safety and accuracy during the first week after acute myocardial infarction.
Methods and Results Multistage dobutamine-atropine stress echocardiography was performed in 232 patients (age, 58±13 years; 58 women) at 5±2 days after acute myocardial infarction. The peak heart rate was 116±20 bpm. There were no episodes of sustained ventricular tachycardia, myocardial infarction, or death. Atropine with dobutamine was tolerated well. Coronary angiography was performed in 206 patients (89%). There were 171 patients (83%) with infarct artery stenosis of ≥50% and 114 patients (55%) with multivessel disease. Ischemic or biphasic responses in the infarction zone were 82% (140 of 171) sensitive and 80% (28 of 35) specific for residual stenosis. Sensitivity was similar for occluded arteries (77%, 36 of 47) and patent but stenotic arteries (84%, 104 of 124). Wall motion abnormalities outside the infarction zone were specific (97%, 89 of 92) and moderately sensitive (68%, 77 of 114) for multivessel disease. The only determinant of sensitivity for residual infarct artery stenosis was improved wall motion at low dose (P<.01). The determinants of sensitivity for multivessel disease were peak heart rate and infarct size (P<.01).
Conclusions Dobutamine-atropine stress echocardiography was safely used to detect residual infarct artery stenosis and multivessel disease during the first week after acute myocardial infarction. The test may be very effective for evaluating patients with acute myocardial infarction because sensitivity for residual stenosis and multivessel disease was maximal in the high-risk subsets of patients with viable, jeopardized myocardium and large infarct size.
Left ventricular function and the extent of coronary artery disease are important determinants of outcome after acute myocardial infarction.1 2 3 4 5 6 Residual stenosis of the infarct artery is common (70% to 90%) after acute myocardial infarction7 8 9 but may be predictive of outcome only in patients with jeopardized myocardium and inducible ischemia.1 9 10 11 12 13 14 15 16 17 In contrast, multivessel coronary artery disease is an independent predictor of adverse outcome.4 5 10 11 Recurrent cardiac events are most common during the first 3 to 6 months after acute myocardial infarction.6 17 Thus, patient outcome may be improved by the early detection of multivessel coronary artery disease and jeopardized viable myocardium in the infarction zone.1 2 3 4 5 9 10 11
Dobutamine-atropine stress echocardiography is increasingly being used to identify myocardial viability and coronary artery disease.18 19 20 21 22 23 24 25 26 27 28 29 30 31 Its safety and accuracy for the detection of coronary artery disease have been documented in patients with suspected coronary artery disease.18 19 20 21 22 23 24 25 26 Low-dose (4 to 10 μg·kg−1·min−1) dobutamine echocardiography has been shown to accurately measure ventricular function and infarction size and to identify reversible dysfunction after acute myocardial infarction.27 28 29 30 Dobutamine-atropine stress echocardiography has not been used to evaluate patients during the first week after acute myocardial infarction; its safety and accuracy for the residual stenosis of the infarct artery and multivessel disease are unclear in these patients. Treatment with β-adrenergic antagonists is common after acute myocardial infarction, so dobutamine infusion with atropine is the optimal stress protocol.18
The aims of the present study were to (1) document the safety of dobutamine-atropine stress echocardiography within the first week after acute myocardial infarction, (2) investigate the accuracy of induced wall motion abnormalities in the infarction zone for residual stenosis of the infarct-related artery, and (3) document the accuracy of wall motion abnormalities outside the infarction zone for multivessel coronary artery disease. To investigate these aims, 232 patients underwent dobutamine-atropine stress echocardiography during the first week after acute myocardial infarction.
Between July 1991 and June 1995, 232 patients admitted for acute myocardial infarction were prospectively enrolled in the study. All patients gave informed consent. The protocol was approved by the Institutional Review Committee of the Medical College of Wisconsin. Myocardial infarction was documented by chest pain, serum creatine kinase and MB fraction levels >2 SDs above normal, ST-segment elevation or depression ≥1.0 mm in ≥2 contiguous leads, and a wall motion abnormality. Another 148 eligible patients were excluded due to patient or physician refusal (43), referral >7 days after acute infarction (30), technically inadequate echocardiography (5), hemodynamic instability for >7 days (50), or sustained ventricular tachycardia >24 hours after admission (20).
Dobutamine-Atropine Echocardiography Protocol
Dobutamine-atropine echocardiography was performed 2 to 7 days after acute myocardial infarction with continuous 12-lead ECG monitoring. The use of β-adrenergic antagonists was continued. The stages of dobutamine infusion were 5, 10, 20, 30, and 40 μg·kg−1·min−1. Intravenous atropine (0.2 to 0.4 mg every 2 minutes to a maximum of 2 mg) was infused to achieve peak heart rates of >120 bpm (1) if the heart rate was submaximal at a maximal dose of dobutamine or (2) if cyclic variability in heart rate of >10 bpm, hyperdynamic wall motion (end-systolic left ventricular diameter of <1 cm), or nausea with retching occurred at submaximal doses of dobutamine. Stage duration was 5 to 10 minutes with imaging after 5 minutes. Blood pressure was measured at 5 minutes of each stage.
End points were maximum dose, heart rate of ≥120 bpm,23 limiting chest pain, headaches, severe nausea, vomiting, ≥2 mm of ST elevation or depression compared with baseline in ≥2 leads, hypotension (systolic blood pressure <90 mm Hg), hypertension (systolic blood pressure ≥240 mm Hg), ventricular tachycardia (≥4 complexes at cycle lengths <600 ms), or sustained supraventricular tachyarrhythmias. Esmolol (0.1 to 0.5 mg/kg IV every 2 minutes up to 1.5 mg/kg) and/or nitroglycerin (0.4 mg SL every 5 minutes up to 3 doses) were administered after the infusion was stopped if chest pain was severe or did not resolve within 4 minutes.
Six echocardiographic views (parasternal long- and short-axis, apical four-chamber, two-chamber, long-axis, and short-axis views) were videotaped at rest and each dose of dobutamine and atropine. Images were digitized on-line at four stages (rest, 5 μg·kg−1·min−1, 10 μg·kg−1·min−1, and peak dose) with a CineView (Prizm Imaging) R-wave–triggered acquisition system and stored in a quadscreen, continuous-loop format on 3.5-in floppy disks.23 27
The digitized images were analyzed by two experienced readers without knowledge of clinical, ECG, or angiographic patient data. To minimize bias, these echocardiograms were randomly mixed with studies from 288 patients with suspected disease. When there was disagreement, a third investigator viewed the images, and differences were resolved by consensus. Videotape recordings were not routinely used but were available. Images at each stage were directly compared and analyzed with the use of the standard 16-segment model and scoring system (1, normal; 2, hypokinesis; 3, akinesis; 4, dyskinesis).22 27 Normal was considered to be normal systolic wall thickening; hypokinesis was reduced thickening; akinesis was near or total absence of thickening; and dyskinesis was endocardial excursion away from the lumen and systolic thinning.
Infarction zone segments were identified as previously described.23 Segments were assigned to the left anterior descending, left circumflex, and right coronary arterial distributions (Fig 1⇓) according to the vascular distribution of segments. Infarction zone segments were identified by resting dysfunction if only one vascular territory was abnormal or by the location of ECG changes if more than one vascular territory was abnormal.
Global wall motion score index at each stage was calculated according to the standard formula: Sum of the Segment Scores/Number of Segments Scored. Dobutamine-responsive wall motion in the infarction zone was defined as improved wall thickening in ≥2 contiguous segments at any stage compared with rest.27 Infarction size was defined as the number of akinetic or dyskinetic segments at low dose (5 and 10 μg/kg/min).30 An ischemic response was defined as decreased wall thickening in ≥2 contiguous segments at peak dose without an improvement at low dose.31 A biphasic response was defined as improved wall thickening in ≥2 contiguous segments from rest to low dose followed by decreased wall thickening in ≥2 contiguous segments from low to peak dose.31 Improved segmental thickening was defined as (1) hypokinetic segments that normalize and (2) akinetic or dyskinetic segments that become hypokinetic or normal. Decreased segmental thickening was defined as (1) normal segments that become hypokinetic, akinetic, or dyskinetic and (2) hypokinetic segments that become akinetic or dyskinetic. Changes from akinesis to dyskinesis at peak dose were also evaluated as a criterion for residual stenosis of the infarct artery, but changes from dyskinesis to akinesis at low dose were considered to be unchanged.30 Changes from dyskinesis to akinesis at low dose are very specific for nonviability.30 Multivessel disease was defined as abnormal wall thickening in ≥2 contiguous segments in one or more remote vascular territory. Single-segment changes are often false-positives,32 but the criterion of changes in ≥2 segments was validated by comparison with the criteria of 1 and 3 segments in infarction and remote territories.
Coronary angiography was done according to the Judkins technique in 206 patients within 2 days of dobutamine-atropine echocardiography at the discretion of the staff cardiologist. Angiograms were analyzed by two experienced investigators without knowledge of other data. The infarct artery was identified on the basis of coronary anatomy, lesion morphology, and the location of the acute ECG changes and wall motion abnormality.33 Percent luminal diameter stenosis of all coronary stenoses was determined according to the caliper technique.34 The diameter of the most stenotic region was compared with that of the most normal-appearing proximal region. Stenosis was ≥50% luminal diameter stenosis. Vessels with TIMI grade 0 flow were considered to be occluded.33
Continuous data are expressed as mean±SD. χ2 analysis and Fisher’s exact test were used to compare categorical clinical, echocardiographic, and angiographic data. Continuous data were compared using one-way ANOVA and Bonferroni’s t test to test the significance of different pairs of mean values. Repeated-measures ANOVA and Bonferroni’s t test were used to evaluate changes in hemodynamics during dobutamine-atropine echocardiography. A two-tailed value of P≤.05 was considered significant.
There were 174 men and 58 women enrolled in the study (mean age, 58±13 years; peak creatine kinase, 2155±2043 IU/mL). Q-wave and anterior myocardial infarction occurred in 131 and 98 patients, respectively. Thrombolytic therapy was used in 127 patients, and β-adrenergic–blocking agents were used in 117 patients. Thirty-six patients had had a previous clinical myocardial infarction.
Coronary angiography was performed in 206 patients (89%). All clinical data and echocardiographic results were similar for patients who did and for those who did not undergo angiography, except for the prevalence of prior myocardial infarction (0 of 26 versus 36 of 206, P<.01), thrombolytic therapy (5 of 26 versus 120 of 206, P<.01), and anterior infarction (6 of 26 versus 92 of 206, P<.05).
The infarct artery was the left anterior descending coronary in 92 patients, the left circumflex in 41, and the right coronary in 73. Mean luminal diameter stenosis was 76±27%. Residual stenosis was found in 83% of the patients (171 of 206). The stenosis was 100% in 47 patients, 70% to 99% in 108, and 50% to 69% in 16. Collaterals were noted in 26 patients (13%). Multivessel disease was found in 114 patients (55%), including 82 with two-vessel disease (24 with left circumflex and right coronary artery disease, 22 with left anterior descending coronary and left circumflex disease, and 36 with left anterior descending and right coronary artery disease) and 32 with three-vessel disease.
Dobutamine-atropine echocardiography was performed at 4.5±1.6 days after acute myocardial infarction. The peak dobutamine dose was 26±10 μg·kg−1·min−1. Atropine (0.2 to 1.6 mg) was used in 76 patients. The peak heart rate and systolic blood pressure were 116±20 bpm (68 to 190 bpm) and 135±29 mm Hg (80 to 240 mm Hg), respectively. ST elevation and depression (≥1 mm) occurred in 102 patients (42%) and 36 patients (16%), respectively. End points were heart rate of ≥120 bpm in 126 patients (54%), maximal dose in 21 (9%), chest pain in 15 (7%), junctional tachycardia or atrial fibrillation in 5 (2%), nonsustained (five to seven beats) ventricular tachycardia in 7 (3%), multiple inducible wall motion abnormalities in 17 (7%), ST elevation or depression (≥2 mm) in 32 (14%), severe nausea in 4 (2%), vomiting in 1 (0.5%), hypertension in 1 (0.5%), and hypotension in 3 (1%).
Dobutamine infusion and atropine boluses were tolerated well without episodes of urinary retention, hallucinations, or narrow-angle glaucoma in the 232 study patients. Atropine did not increase the incidence of arrhythmias or adverse effects. Dobutamine infusion produced nausea in 9 patients (4%) and vomiting in only 2 patients, but 4 patients achieved maximal heart rates. Forty-four patients (19%) experienced chest pain, including 29 at maximal and 15 at submaximal heart rates. Only 3 required treatment with intravenous esmolol and/or sublingual nitroglycerin. Seven patients developed hypotension and 1 developed hypertension, but 3 achieved maximal heart rates. Blood pressure rapidly normalized with cessation of the infusion. There were no hemodynamically significant arrhythmias. Fifty-one patients (22%) developed frequent premature ventricular complexes (≥6/min). Three patients (2%) developed asymptomatic junctional tachycardia that resolved within minutes after cessation of the infusion. Two patients (1%) developed atrial fibrillation that resolved within 1 to 2 hours after cessation of the infusion. All 5 patients with sustained supraventricular arrhythmias achieved their target maximal heart rate. Seven patients (3%) had asymptomatic five- to seven-beat runs of nonsustained ventricular tachycardia that did not require therapy.
Analysis of wall motion was restricted to the 206 patients who underwent coronary angiography. At rest, mean global wall motion score index was 1.70±0.38. At low dose, infarction zone wall motion worsened in 4 (2%), did not change in 74 (36%), and improved in 128 (62%). Infarction size was large (≥4 akinetic or dyskinetic segments at low dose) in 90 patients and small to moderate (≤3) in 116. Infarction zone wall motion demonstrated sustained improvement at low and peak dose in 20 patients (10%), unchanged wall motion in 39 (19%), an ischemic response in 39 (19%), and a biphasic response in 108 (52%; P<.01 versus ischemic response).
In these patients, resting or inducible wall motion abnormalities were detected outside the infarction zone in 39% of patients (80 of 206). Sixty-two patients demonstrated a wall motion abnormality in one of the two territories outside the infarction zone, and 18 demonstrated abnormalities in both territories. The distributions of the wall motion abnormalities in the 62 patients with abnormalities in the infarction zone and one remote territory were the right coronary and left circumflex territories in 16, the left anterior descending coronary and left circumflex territories in 13, and the left anterior descending and right coronary territories in 33.
Detection of Residual Stenosis of the Infarct Artery
The dobutamine-atropine echocardiographic findings of biphasic or ischemic responses were most sensitive and specific for residual infarct artery stenosis (Table 1⇓). Ischemic responses were specific for residual stenosis. Biphasic responses were also specific but more sensitive (P<.01). Therefore, the comparison of peak dose images with not only rest but also low dose (ECHO algorithm) significantly improved (P<.01) sensitivity without altering specificity. Unchanged wall motion or sustained improvement was common (18 and 10, respectively) in the 35 patients without residual stenosis and rare (21 and 10, respectively) in the 171 patients with residual stenosis. Chest pain and ST depression were specific but insensitive (P<.01 versus ECHO algorithm). ST elevation was also insensitive (P<.01 versus ECHO algorithm). An algorithm of chest pain and ST changes was not specific or sensitive (P<.01 versus ECHO algorithm).
Dobutamine-atropine echocardiography did not differentiate infarct artery occlusion from patent but stenotic arteries (50% to 99%; Table 2⇓). Ischemic and biphasic responses were as common in patients with occluded arteries as in those with 70% to 99% or 50% to 69% stenosis. Responses in patients with occluded arteries were not related to angiographic collaterals. Wall motion score indices and the number of abnormal, akinetic, or dyskinetic segments were similar in patients with occluded and stenotic arteries at all stages.
Vascular territory had no effect on sensitivity or specificity for the detection of residual stenosis (Fig 2⇓). Sensitivity and specificity were similar for residual stenosis in the left anterior descending coronary, left circumflex, and right coronary vascular territories.
Dobutamine-atropine echocardiography was insensitive for residual stenosis only in patients with unchanged wall motion at low dose (Table 3⇓). Ischemic or biphasic responses were specific for residual stenosis in this group, but sensitivity was much less than that in patients responding to low dose. Unchanged wall motion at low dose was the only independent cause of false-negative studies. All four patients with ischemic responses at low dose had residual stenosis. Submaximal stress (peak heart rate <120 bpm) did not affect sensitivity or specificity. Infarct size also had no effect on sensitivity or specificity. Studies were more commonly (P<.05) terminated for ST-segment depression or elevation in false-negative studies. End points in the 31 patients with false-negative studies were heart rate of ≥120 bpm in 13, chest pain in 4, ≥2 mm of induced ST elevation in 7, ≥2 mm of induced ST depression in 6, and maximal dose in 1.
Finally, the criterion of changes in ≥2 contiguous infarction zone segments optimized sensitivity and specificity (82%, 140 of 171; and 80%, 28 of 35, respectively). The addition of patients demonstrating changes in only one segment minimally changed sensitivity (86%, 147 of 171) but reduced specificity (54%, 19 of 35; P=.05 versus ≥2 segments). The addition of patients changing from akinesis to dyskinesis at peak dose also did not change sensitivity (84%, 143 of 171) but tended to reduce specificity (66%, 23 of 35). The strict criterion of changes in ≥3 segments was less sensitive (66%, 113 of 171; P<.01 versus ≥2 segments) but as specific (86%, 30 of 35).
Detection of Multivessel Disease
Wall motion abnormalities outside the infarction zone were very specific and moderately sensitive for multivessel disease (Table 4⇓). Sensitivity tended to be higher (P=.08) in patients with three-vessel disease (81%, 26 of 32) than in those with two-vessel disease (62%, 51 of 82). Sensitivity was higher (P<.01) at peak heart rates of ≥120 bpm than at rates of <120 bpm. Sensitivity was highest in patients with large (≥4 segments) infarct size and lowest (P<.01) in patients with small to moderate (≤3 segments) infarct size. Both submaximal stress and small to moderate infarct size independently (P<.01) contributed to false-negative studies. Peak heart rates were submaximal in the majority of the false-negative studies (73%, 27 of 37). Only 10 of the patients with false-negative studies achieved heart rates of ≥120 bpm (P<.01 versus patients with true-positive studies). The 27 other false-negative studies were terminated at submaximal heart rates due to ≥2 mm of ST elevation in 13, ≥2 mm of ST depression in 2, chest pain in 10, and inadequate chronotropic response at a maximal dose in 2.
Again, the criterion of abnormal wall thickening in ≥2 contiguous segments in one or more vascular territory outside the infarction zone optimized sensitivity and specificity for multivessel disease at 68% (77 of 114) and 97% (89 of 92) of patients, respectively. The criterion of abnormal wall thickening in ≥1 segment was as sensitive (70%, 80 of 114) but less specific (82%, 75 of 92; P<.01 versus ≥2 segments). The criterion of abnormal wall thickening in ≥3 segments was less sensitive (44%, 50 of 114; P<.01 versus ≥2 segments) but as specific (97%, 89 of 92).
Interobserver and Intraobserver Variability
The two observers agreed that resting infarction zone wall motion was abnormal in 99% of patients (204 of 206) who underwent angiography. The scoring of segments as normal (98%, 1993 of 2030), hypokinetic (92%, 423 of 460), or akinetic/dyskinetic (95%, 1150 of 1210) was highly reproducible at rest. Readings agreed regarding (1) the extent (±1 segment) of infarction zone dysfunction in 94% (194 of 206), (2) changes in the infarction zone at low dose in 95% (196 of 206) and at peak dose in 94% (193 of 206), and (3) wall motion at rest and at peak dose outside the infarction zone in 94% of patients (194 of 206). Differences were resolved by consensus in 13 patients (6%).
Intraobserver variability was assessed by one reader in a subset of 64 patients. Infarction zone resting wall motion was concordantly abnormal in 100% (64 of 64). The scoring of segments at rest as normal (99%), hypokinetic (93%), or akinetic/dyskinetic (96%) was reproducible. Interpretations were also reproducible regarding (1) the extent of infarction zone dysfunction in 95% (61 of 64), (2) changes in infarction zone wall motion at low dose in 94% (60 of 64) and at peak dose in 94% (60 of 64), and (3) wall motion outside the infarction zone in 95% of patients (61 of 64).
The results in the 288 patients with suspected coronary artery disease who underwent angiography were sufficiently similar to the findings in the study population to eliminate observer bias. Resting wall motion abnormalities were present in 144 patients (50%). Sensitivity (87%, 181 of 209) and specificity (89%, 70 of 79) for ≥50% stenosis were similar (P=NS versus acute myocardial infarction). The reproducibility of readings was also similar (95%, 274 of 288). Differences were resolved by consensus in only 5% (14 of 288). Ischemic (104 of 111) and biphasic (39 of 41) responses were as predictive of disease and sustained improvement of the absence of disease (70 of 98).
Safety of Dobutamine-Atropine Stress Echocardiography After Acute Myocardial Infarction
The safety of dobutamine-atropine stress testing has not been documented early after acute myocardial infarction. Prior studies have excluded patients with acute (<1 week) myocardial infarction.19 20 21 Mertes et al19 reported no serious complications (ie, deaths, myocardial infarction, ventricular tachycardia or fibrillation) in 1118 patients with suspected coronary artery disease or remote myocardial infarction. Frequent (≥6/min) premature ventricular complexes occurred in 15%, nonsustained ventricular tachycardia occurred in 4%, and angina occurred in 19%. Intravenous esmolol and nitroglycerin were used in 2% to 4%. Poldermans et al20 reported no deaths or myocardial infarctions in 650 patients with remote myocardial infarction or suspected coronary disease. Frequent premature ventricular complexes occurred in 10%, angina occurred in 4%, ventricular fibrillation occurred in 0.2%, nonsustained (<10 beats) ventricular tachycardia occurred in 2%, sustained ventricular tachycardia occurred in 2%, and atrial fibrillation occurred in 1.2%. A multicenter trial with 2799 patients with remote myocardial infarction or suspected coronary artery disease reported serious complications in 0.5% (sustained ventricular tachycardia, 0.1%; ventricular fibrillation, 0.07%; myocardial infarction, 0.1%; hypotension, 0.04%; and atropine-related hallucinations, 0.2%), nonsustained ventricular tachycardia in 4%, and supraventricular tachycardia in 2% of participants.21
The dobutamine-infusion protocol of this study was tailored to its half-life of ≈2 minutes and equilibrium blood levels occurring at 5 to 10 minutes.35 All prior studies used 3-minute stages, peak doses of 30 to 50 μg·kg−1·min−1, and atropine after the maximum dobutamine dose. The stepwise increase in dosing before equilibrium did not maximize the effects of each dose, so infusion rates were higher (35 to 40±10 μg·kg−1·min−1, P<.01) than those used in the present study.
The results of the present study demonstrated that dobutamine-atropine stress echocardiography in 5- to 10-minute stages was safe during the first week after myocardial infarction. ST elevation was more common in this study, but the incidence of chest pain, frequent premature ventricular complexes, nonsustained ventricular tachycardia, and supraventricular tachycardia was similar. The longer stage duration lowered mean peak dose and resulted in no deaths, myocardial infarctions, or sustained ventricular arrhythmias. Severe angina occurred in only 2 patients, and both stabilized with the use of esmolol and nitroglycerin. Atropine did not increase arrhythmias, angina, or side effects. On the basis of these data, the incidence of severe complications (death, myocardial infarction, or sustained ventricular arrhythmias) is <1%.
Identification of Stenosis of the Infarct-Related Artery
Residual stenosis of the infarct artery is common (70% to 90%) after acute myocardial infarction.7 8 9 Early detection may improve patient management if accuracy is high in patients with extensive dysfunction and viability. This group may benefit most from early revascularization of the infarct artery.4 5 6 12 13 14 15 17 36
Previous studies have not investigated the accuracy of dobutamine-atropine stress echocardiography for the early detection of residual stenosis after acute myocardial infarction.18 19 20 21 22 23 24 25 26 One study of 40 patients at 1 month after myocardial infarction reported that worsening or unchanged wall motion from rest to peak dose was sensitive and specific.24 Low-dose imaging was not done. Another small study of 51 patients at 1 to 2 weeks after myocardial infarction restricted analysis to the 36 patients with dobutamine-responsive wall motion at low dose.25 Worsening wall motion from low to peak dose was sensitive, but the specificity was not reliable due to the small number of patients without residual stenosis (6). In neither study was atropine used.
In the present study, there were more study patients, atropine was used when appropriate, and all patients were studied within the first week after acute myocardial infarction. The algorithm of ischemic or biphasic responses was sensitive and specific for residual infarct artery stenosis. The multistage protocol enhanced the accuracy because biphasic responses were more sensitive than ischemic responses. In contrast to the results of Takeuchi et al,24 unchanged wall motion was not predictive of residual stenosis.
The results of the present study also conflict with those of some smaller trials. The strict two-segment criterion optimized accuracy for residual stenosis.24 25 26 Changes from akinesis to dyskinesis were not predictive of residual stenosis. The majority of patients demonstrating changes from akinesis to dyskinesis at peak dose had false-positive studies (5 of 8), indicating that these changes probably resulted from alterations in loading conditions or hypercontraction of normal myocardium.30 37
Dobutamine-atropine echocardiography was most sensitive when wall motion improved at low dose, indicative of viability.27 28 29 30 In contrast to studies in patients with suspected disease,23 accuracy was not altered by peak heart rate, infarction size, or location. False-negative studies were most common in patients with unchanged wall motion at low dose. Thus, accuracy was highest in the important subgroup of patients with large wall motion abnormalities and viability.12 13 14 15
The multistage protocol allowed detection of residual stenosis but not differentiation of occluded from patent but stenotic arteries. Resting infarction zone dysfunction was similar. Findings at low and peak dose were also similar. Angiographic collaterals also were not predictive of findings in patients with occluded arteries. These data are consistent with the poor sensitivity of angiographic collaterals for collateral myocardial blood flow.38
Detection of Multivessel Coronary Artery Disease
Multivessel coronary artery disease is strongly predictive of adverse outcome after acute myocardial infarction.4 5 6 12 Multiple wall motion abnormalities during dobutamine-atropine stress echocardiography were shown to identify multivessel disease in one study of 101 patients with suspected coronary artery disease.22 Its accuracy during the first week after myocardial infarction has not been investigated. In a small study, 30 patients were evaluated at 1 to 2 weeks after myocardial infarction, and wall motion abnormalities outside the infarction zone were reported as sensitive and specific for multivessel disease.26 The model of vascular territories was atypical and used right ventricular ischemia to identify right coronary artery disease. Dobutamine was infused in 3-minute stages up to 40 μg·kg−1·min−1. Atropine was not used.
The present study in a large cohort of patients showed that wall motion abnormalities outside the infarction zone were moderately sensitive and highly specific for multivessel coronary artery disease during the first week after acute myocardial infarction. The data also demonstrate that the strict two-segment criterion optimized accuracy for multivessel disease.24 25 26 Submaximal stress and small to moderate infarct size contributed to false-negative studies. Sensitivity was high at heart rates of ≥120 bpm and in patients with large infarct size and similar to that reported in patients with suspected coronary disease.22 Because infarct size is strongly predictive of outcome,2 15 39 dobutamine-atropine echocardiography was most sensitive in high-risk patients.
Not all patients underwent angiography, but the effect was probably minimal. The only differences in the 11% of patients without angiography were lower prevalences of anterior infarction, thrombolytic therapy, and prior infarction. Dobutamine-atropine echocardiographic findings in these patients were similar to those in patients who underwent angiography. Angiographic analysis was done by the caliper technique rather than by quantitative angiography, but the caliper technique and quantitative angiography have been shown to produce comparable results.34 40
Dobutamine-atropine echocardiography has not been directly compared with other imaging stress tests after acute myocardial infarction. Comparative trials are needed. Our laboratory is a high-volume facility, so the results may not be applicable to those of low-volume laboratories.41 Multicenter trials are needed to document the reproducibility of these results and further establish its safety.
Finally, wall motion analysis was done by qualitative or semiquantitative techniques rather than by quantitative techniques. This method remains the standard for analysis because no effective quantitative method has been developed.
Conclusions and Clinical Implication
Multistage dobutamine-atropine stress echocardiography in 5- to 10-minute stages was safe and specific for the early detection of residual stenosis of the infarct artery and multivessel disease after acute myocardial infarction. Biphasic and ischemic responses in the infarction zone were the most sensitive findings for residual stenosis of the infarct artery. ST-segment changes were common, contributed to false-negative studies, and should not be used as an end point. Sensitivity for residual stenosis was highest in patients with jeopardized viable myocardium. Sensitivity for multivessel disease was highest in patients with large infarct size and peak heart rates of ≥120 bpm. Thus, accuracy was greatest in patients whose outcome may be altered by early revascularization.
This work was supported in part by the Kyle Company, Mequon, Wisc.
- Received September 3, 1996.
- Revision received October 28, 1996.
- Accepted November 23, 1996.
- Copyright © 1997 by American Heart Association
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