How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.

OBJECTIVES: This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. BACKGROUND: Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. METHODS: One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. RESULTS: The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). CONCLUSIONS: We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.

Comparative ability of dobutamine and exercise stress in inducing myocardial ischaemia in active patients.

OBJECTIVE: To compare the ability of dobutamine and exercise stress to induce myocardial ischaemia and perfusion heterogeneity under routine clinical circumstances. DESIGN: 86 active patients without previous myocardial infarction were studied by dobutamine and exercise stress protocols and coronary angiography. During both tests patients underwent electrocardiography, digitised echocardiography, and perfusion scintigraphy using Tc-99m methoxybutylisonitrile (MIBI) single photon emission computed tomography. MAIN OUTCOME MEASURE: Coronary disease defined as an ST segment depression of > or = 0.1 mV, a resting or stress induced perfusion defect, or a resting or stress induced wall motion abnormality on exercise and dobutamine stress testing. RESULTS: Dobutamine stress was submaximal in 51 patients because of ingestion of beta adrenoceptor blocking agents on the day of the test (n = 25) or failure to attain the peak dose owing to side effects (n = 28). Exercise was limited in 23 patients by non-cardiac symptoms. The peak heart rate with dobutamine was less than that attained with exercise (105 (25) v 132 (24) beats/min, P < 0.0001); the response to maximal dobutamine stress significantly exceeded that to submaximal stress. Peak blood pressure was greatest with exercise (206 (27) v 173 (25) mm Hg, P < 0.001), values at maximal and submaximal dobutamine stress being comparable. Electrocardiographic evidence of ischaemia was induced less frequently by dobutamine than exercise (32% v 77% of the 56 patients with significant coronary disease, P < 0.01), as was abnormal wall motion (54% v 88%, P < 0.001). Ischaemia was induced more readily with maximal stress of either type; thus the sensitivities of dobutamine and exercise echocardiography were comparable only in patients undergoing a maximal dobutamine testing (73% v 77%, NS). Perfusion heterogeneity was induced in 58% of patients with coronary disease at submaximal dobutamine stress, 73% at maximal dobutamine stress, and 73% at exercise stress (NS). Among 30 patients without coronary stenoses, normal function was obtained in 83% of echocardiography studies with dobutamine and in 80% with exercise (NS). Normal perfusion was identified in 70% of these patients at exercise MIBI, and 68% at dobutamine stress (NS). CONCLUSIONS: In a group of patients studied under normal clinical circumstances antianginal treatment and inability to complete the stress protocol are frequent and compromise the capacity of dobutamine stress to induce ischaemia. In contrast, the induction of perfusion heterogeneity is less susceptible to submaximal stress.

Relation between myocardial blood flow and the severity of coronary-artery stenosis.

BACKGROUND: We assessed the relation between the severity of stenosis in a coronary artery and the degree of impairment of myocardial blood flow. Studies in laboratory animals have shown that as the degree of coronary-artery stenosis increases, the maximal coronary flow measured after maximal vasodilation progressively decreases, with a concomitant decrease in basal flow. However, this relation has not been carefully documented in humans through measurement of myocardial blood flow. METHODS: We studied 35 patients with single-vessel coronary artery disease and normal left ventricular function and 21 age-matched controls. Regional myocardial blood flow in the area supplied by the stenosed artery was measured by positron-emission tomography with oxygen-15-labeled water while the subject was at rest (basal flow) and during hyperemia induced by the intravenous administration of the vasodilator adenosine (140 micrograms per kilogram of body weight per minute) or dipyridamole (0.56 mg per kilogram). RESULTS: The mean (+/- SD) basal myocardial blood flow was 1.14 +/- 0.42 ml per minute per gram of tissue in the patients and 1.13 +/- 0.26 ml per minute per gram in the controls; during hyperemia, myocardial flow was 2.10 +/- 1.16 and 3.37 +/- 1.25 ml per minute per gram (P < 0.001), respectively. Basal flow was unchanged regardless of the severity of stenosis, expressed as a percentage of the diameter of the affected vessel (range of degrees of stenosis, 17 to 87 percent). In contrast, flow during hyperemia correlated inversely and significantly with the degree of stenosis and correlated directly with the minimal luminal diameter. The coronary vasodilator reserve (defined as the ratio of flow during hyperemia to flow at base line) began to decline when the degree of stenosis was about 40 percent and approached unity when stenosis was 80 percent or greater. CONCLUSIONS: In humans, basal myocardial blood flow remains constant regardless of the severity of coronary-artery stenosis. However, during hyperemia, flow progressively decreases when the degree of stenosis is about 40 percent or more and does not differ significantly from basal flow when stenosis is 80 percent or greater.

Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography.

BACKGROUND: Experimental studies have shown that fractional flow reserve (defined as the ratio of maximal achievable flow in a stenotic area to normal maximal achievable flow) can be calculated from coronary pressure measurements only. The objectives of this study were to validate fractional flow reserve calculation in humans and to compare this information with that derived from quantitative coronary angiography. METHODS AND RESULTS: Twenty-two patients with an isolated, discrete proximal or mid left anterior descending coronary artery stenosis and normal left ventricular function were studied. Relative myocardial flow reserve, defined as the ratio of absolute myocardial perfusion during maximal vasodilation in the stenotic area to the absolute myocardial perfusion during maximal vasodilation (adenosine 140 micrograms.kg-1 x min-1 intravenously during 4 minutes) in the contralateral normally perfused area, was assessed by 15O-labeled water and positron emission tomography (PET). Myocardial and coronary fractional flow reserve were calculated from mean aortic, distal coronary, and right atrial pressures recorded during maximal vasodilation. Distal coronary pressures were measured by an ultrathin, pressure-monitoring guide wire with minimal influence on the trans-stenotic pressure gradient. Minimal obstruction area, percent area stenosis, and calculated stenosis flow reserve were assessed by quantitative coronary angiography. There was no difference in heart rate, mean aortic pressure, or rate-pressure product during maximal vasodilation during PET and during catheterization. Percent area stenosis ranged from 40% to 94% (mean, 77 +/- 13%), myocardial fractional flow reserve from 0.36 to 0.98 (mean, 0.61 +/- 0.17), and relative flow reserve from 0.27 to 1.23 (mean, 0.60 +/- 0.26). A close correlation was found between relative flow reserve obtained by PET and both myocardial fractional flow reserve (r = .87) and coronary fractional flow reserve obtained by pressure recordings (r = .86). The correlations between relative flow reserve obtained by PET and stenosis measurements derived from quantitative coronary angiography were markedly weaker (minimal obstruction area, r = .66; percent area stenosis, r = -.70; and stenosis flow reserve, r = .68). CONCLUSIONS: Fractional flow reserve derived from pressure measurements correlates more closely to relative flow reserve derived from PET than angiographic parameters. This validates in humans the use of fractional flow reserve as an index of the physiological consequences of a given coronary artery stenosis.

Optimal use of dobutamine stress for the detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both?

OBJECTIVES: This study was conducted to examine the efficacy of dobutamine stress two-dimensional echocardiography and perfusion scintigraphy for the detection of coronary artery disease in routine practice, to establish the causes of erroneous results and to derive appropriate criteria for the selection of either or both tests. BACKGROUND: Dobutamine stress combined with echocardiography or perfusion scintigraphy may be used to detect coronary artery disease. Although both imaging approaches have demonstrated similar levels of accuracy, it is not known whether there may be particular indications for the use of one or the other technique or a rationale for their combination. METHODS: Two hundred seventeen patients without previous infarction were studied prospectively with dobutamine stress echocardiography and technetium-99m methoxy isobutyl nitrile (sestamibi) single-photon emission computed tomography at the time of diagnostic coronary angiography. The presence of coronary stenoses of > or = 50% diameter was compared with the presence of rest or stress-induced abnormalities of perfusion and regional function. The extent of these abnormalities was correlated with an equivalent score of extent of angiographic disease. RESULTS: Significant coronary artery disease was found in 142 patients; 102 (72%) were identified by dobutamine echocardiography and 108 (76%, p = NS) by perfusion imaging. In 75 patients without significant disease, the specificity of dobutamine echocardiography was 83% compared with 67% for scintigraphy (p = 0.05). Echocardiographic sensitivity was lower in patients unable to complete the test because of side effects (n = 64) than in the remainder (59% vs. 77%, p = 0.02); this influence was less apparent with scintigraphy (71% vs. 78%, p = NS). Selective use of scintigraphy in the 31 patients with a negative submaximal stress echocardiogram led to a sensitivity of 80% for this combination. Patients with left ventricular hypertrophy accounted for most of the difference in specificity between echocardiography and scintigraphy (94% vs. 59%, p = 0.02). Their respective accuracies were 76% and 73%. CONCLUSIONS: Dobutamine stress echocardiography and perfusion scintigraphy have equivalent accuracy. In patients with left ventricular hypertrophy, echocardiography appears to be the test of choice. Selective use of sestamibi scintigraphy in patients with a negative submaximal echocardiogram enhances the accuracy of stress echocardiography alone.

Diagnosis of coronary artery disease in elderly patients: safety and efficacy of dobutamine echocardiography.

Coronary artery disease may be difficult to diagnose in the elderly because its clinical symptomatology is frequently atypical and because the performance of submaximal tests makes exercise stress testing sometimes unreliable. Dobutamine stress testing may be a useful alternative in such patients. This study compared the safety and accuracy of dobutamine stress echocardiography in 73 'young' (< 60 years old) and 63 'old' (> or = 60 years old) patients without previous myocardial infarction undergoing diagnostic coronary angiography. The sensitivity in young patients (79%, (67-91, 95% CI)) was similar to that in old patients (80% (69-91, 95% CI)). Similar levels of specificity (88% (75-101, 95% CI) vs 75% (54-96, 95% CI)) were found in the two groups. Both groups showed a trend to a higher sensitivity for multi-vessel disease than for single-vessel disease. No major side effect occurred during the entire study and peak dose (40 micrograms.kg-1.min-1) was attained with similar frequency in both groups (56% vs 49%). Minor side effects occurred equally in 'young' and 'old' patients and never persisted more than a few minutes after ending the first infusion of dobutamine. Dobutamine echocardiography appears to be safe and accurate for the detection of coronary artery disease regardless of age.

Selection of the optimal nonexercise stress for the evaluation of ischemic regional myocardial dysfunction and malperfusion. Comparison of dobutamine and adenosine using echocardiography and 99mTc-MIBI single photon emission computed tomography.

BACKGROUND: The mechanisms of action of exercise-simulating and vasodilator stressors support their combination with imaging techniques that evaluate left ventricular function and perfusion, respectively. However, reported accuracies of either pharmacological stress together with two-dimensional echocardiography (2DE) or single photon emission computed tomography (SPECT) of myocardial perfusion are similar. The purpose of this study was to establish the optimal stress for each imaging technique by comparing the results of digitized 2DE and 99mTc-methoxyisobutyl isonitrile (MIBI) SPECT using both dobutamine and adenosine stresses in the same patients and conditions. METHODS AND RESULTS: Ninety-seven consecutive patients without evidence of previous infarction undergoing coronary angiography for clinical indications were studied prospectively. Dobutamine was infused during clinical, ECG, and echocardiographic monitoring in dose increments from 5 to 40 micrograms.kg-1.min-1. Adenosine was infused under the same conditions in doses of 0.10, 0.14, and 0.18 mg.kg-1.min-1. For each protocol, the end points were achievement of peak dose, development of severe ischemia, or intolerable side effects. At peak stress, 20 mCi of MIBI was injected, and SPECT imaging was performed 2 hours later; abnormal poststress images were compared with resting SPECT: Digitized 2DE images were compared qualitatively before, during, and after stress in a cine-loop display. Significant coronary disease (n = 59 patients) was defined by the quantification of > 50% stenosis in a major epicardial vessel. The sensitivity of adenosine 2DE was 58%, less than those of adenosine MIBI (86%, p = 0.001), dobutamine 2DE (85%, p = 0.001), and dobutamine MIBI (80%, p = 0.01). Their respective specificities were 87%, 71%, 82%, and 74% (p = NS). The accuracy of adenosine 2DE was 69%, compared with 80% for adenosine MIBI (p < 0.001), 84% for dobutamine 2DE (p = 0.001), and 77% for dobutamine MIBI (p = 0.005); the latter three did not differ significantly in either sensitivity or accuracy. CONCLUSIONS: This prospective, direct comparison of alternative pharmacological stresses in patients without myocardial infarction shows vasodilator stress scintigraphy and dobutamine stress echocardiography and scintigraphy to share equivalent levels of sensitivity. All three are significantly more sensitive than adenosine stress echocardiography. Dobutamine stress may be used for wall motion or perfusion imaging, but adenosine stress is best combined with perfusion scintigraphy.

Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.

BACKGROUND: Both [13N]ammonia and [15O]water have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation. METHODS AND RESULTS: The two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15O]water-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13N]ammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [15O]water. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13N]ammonia (with metabolite correction) was obtained (y = 3 + 0.78x, r = 0.94). The correlation with microspheres was slightly better with [15O]water (y = -3 + 0.89x, r = 0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions. CONCLUSIONS: Positron emission tomography with appropriate tracer kinetic models using [13N]ammonia and [15O]water provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.