We evaluated the use of adenosine, dobutamine and arbutamine with (99m)Tc-tetrofosmin myocardial perfusion imaging. Forty patients under investigation for suspected coronary artery disease were recruited. Each had a resting scan and two separate stress scans on different days, in a randomized cross-over study. Resultant images were blindly reported in 13 segments per scan as normal, reversible or fixed defects. A score was given (0-3) for segmental defect severity. Haemodynamic responses were as expected for each agent. Subjective side effect scores did not differ overall between agents. Adenosine caused a significantly higher incidence of abnormal taste (54%) than dobutamine and arbutamine (both 23%) and a lower incidence of palpitations (25% vs 69% and 54%, respectively), all P<0.05. Arbutamine caused significantly more chest pain than adenosine (77% vs 46%) though less flushing (35% vs 68%), both P<0.05. Comparison of the results obtained showed highly significant levels of segmental agreement for visual and semi-quantitative analysis between adenosine and arbutamine, kappa value and correlation coefficient of 0.78 and 0.86, respectively, dobutamine and adenosine 0.69 and 0.78, and arbutamine and dobutamine 0.75 and 0.78, all P<0.0001. Adenosine, arbutamine and dobutamine differ in their haemodynamic response and side effect profile but provide highly comparable results during (99m)Tc SPECT imaging.

This investigation examined the prognostic power of first-pass radionuclide angiocardiography (RNA) ejection fraction compared with clinical information and myocardial perfusion imaging in patients undergoing pharmacologic stress testing. The value of RNA and myocardial perfusion imaging in predicting death or nonfatal myocardial infarction (MI) is well established. However, limited information exists on the usefulness of combined myocardial perfusion imaging and RNA to predict prognosis, especially in patients undergoing pharmacologic stress testing.We identified 240 patients who underwent pharmacologic stress testing with myocardial perfusion imaging and combined RNA. The patients were followed for a mean of 1.4 y. Cox proportional hazards models were used to assess the value in predicting death and MI. Multivariable models were generated to assess the independent incremental predictive value of clinical and nuclear imaging variables. Kaplan-Meier survival and event-free survival estimates were examined in patients with low (< or = 45%) versus high (>45%) ejection fractions.Clinical information, myocardial perfusion imaging, and RNA ejection fraction were significant predictors of the death/MI composite outcome (chi(2) = 7.4, 14.0, and 21.8, respectively). The addition of myocardial perfusion imaging to the clinical information provided incremental prognostic information (chi(2) = 15.2). The addition of RNA ejection fraction provided further predictive information (chi(2) = 22.5). However, when RNA ejection fraction was first added to the clinical information, myocardial perfusion imaging had no incremental prognostic value.For hard cardiac events, RNA ejection fraction provides prognostic information besides that provided by clinical and myocardial perfusion imaging. In patients who cannot exercise and are undergoing noninvasive evaluation with pharmacologic stress testing and myocardial perfusion imaging, ejection fraction should be measured simultaneously for risk assessment optimization.

In less than a decade, the use of stress echocardiography has grown dramatically, with both exercise and, for patients unable to exercise adequately, pharmacological stressors, such as dobutamine. A new pharmacological stress agent, arbutamine, administered using a closed-loop computerized feedback system, has recently received approval by the Food and Drug Administration for use with echocardiography and radionuclide myocardial perfusion imaging. This system offers safety and accuracy in echocardiography comparable to the use of dobutamine and promises a number of advantages in terms of ease of use and reductions in personnel and time. A catecholamine specifically designed as a pharmacological stress agent, arbutamine increases heart rate, cardiac contractility, and systolic blood pressure with more balanced chronotropic and inotropic effects than dobutamine. The arbutamine delivery system includes a prefilled syringe of the agent, automatic dosing based on the patient's heart rate response, continuous monitoring of heart rate and blood pressure, a printout of test results, and safety features such as visual and audible warnings and automatic discontinuation of drug after an alarm. The accuracy, safety, convenience, and cost of the arbutamine closed-loop system are likely to make it an attractive agent for echocardiographic diagnosis.

At low doses, dobutamine has potent inotropic, but limited chronotropic, effects-properties that may be necessary for detection of hibernating myocardium. The efficacy of other catecholamines, which have more closely coupled inotropic and chronotropic effects, for the detection of viable myocardium is unknown. This study evaluated the efficacy of arbutamine, a catecholamine with potent chrono-tropic effects, for the detection of viable myocardium in a canine model of hibernating myocardium. Contractile reserve was assessed during stepwise arbutamine infusion (dosages of 2.5, 5, 10, 50, and 100 ng/kg/min) at 3 days (early) and 4 weeks (late) after coronary ligation. Segment shortening, wall thickening, and segmental wall motion were assessed by sonomicrometry and echocardiography. After 4 weeks of occlusion, functional recovery was assessed after revascularization. During the early arbutamine study, the sensitivity for predicting functional recovery was highest at a dosage of 50 ng/kg/min, which also produced tachycardia. The sensitivity was 50% for segment shortening, 20% for wall thickening, and 75% for wall motion score. The late arbutamine study had improved sensitivity. The sensitivity was 100% for segment shortening, 80% for wall thickening, and 90% for wall motion score at a dosage of 50 ng/kg/min. At the late arbutamine study, myocardial perfusion reserve in the ischemic zone of dogs with functional recovery was only mildly reduced (2.0 versus 2.6 in nonischemic zones, P =.53). After coronary occlusion, viable myocardium can be detected with high doses of arbutamine that produce tachycardia. However, the sensitivity of arbutamine stimulation for predicting functional recovery is low early after occlusion, but it is improved by 4 weeks after occlusion with adequate perfusion reserve.

SonoVue is a second-generation ultrasound contrast agent consisting of phospholipid-stabilized microbubbles filled with sulfur hexafluoride, with outstanding stability and resistance to pressure. The efficacy of SonoVue (0.5, 1, 2, 4 mL) was compared with Albunex (doses 0.08 and 0.22 mL/kg) in patients with suspected ischemic disease and suboptimal endocardial-border delineation on unenhanced echocardiography at rest. All the doses resulted in significantly greater increases compared with Albunex in left-ventricular endocardial-border delineation score as well as in the duration of clinically useful contrast effect. The utility of SonoVue in diagnosing ischemic heart disease was also evaluated during pharmacologic stress (arbutamine or dobutamine). SonoVue produced significant increases from baseline in endocardial-border delineation score both at rest and during pharmacologic stress. The possibility of detecting myocardial perfusion defects using SonoVue-enhanced power Doppler and gray-scale harmonic contrast echocardiography associated with continuous and intermittent imaging was assessed in patients with coronary artery disease. The results obtained were comparable with corresponding 99mTc sestamibi single-photon emission computed tomography images. An effective cardiovascular assessment of a patient should also include the evaluation of carotid vessels, intracranial circulation, and renal arteries. SonoVue provided significant improvements in the evaluation of the Doppler signal in terms of diagnosis agreement with reference imaging modality especially for intracranial vessels. The safety profile of SonoVue was evaluated in 1,406 patients. The incidence of adverse events was 10.4%, the great majority of which were of mild intensity and resolved without consequences.

Within the last decade of this millennium, stress echocardiography has been established for the diagnosis and follow-up of coronary artery disease. The basis is the technical development of the echo machines: first, the improved echocardiographic resolution and, second, the digital image storage of a whole cineloop, which may be interpreted frame-by-frame in an ECG synchronized manner for several exercise levels simultaneously. Myocardial ischemia can be detected much earlier by regional contraction abnormalities of the left ventricular myocardium than in conventional ECG exercise tolerance testing explaining the higher sensitivities. Furthermore, the extent and localization, including the correlation with the stenotic coronary anatomy, is possible. The usage of pharmacological stress agents (dobutamine, arbutamine, dipyridamole, adenosine) or electrical stimulating methods (transesophageal, intracardial) allow the examination of patients unable to exercise in similar accuracy.

Episodes of stress-induced myocardial ischemia in patients with coronary artery disease (CAD) may cause increases of QT dispersion (QTd).Aim of this study was to analyze the effect of increasing heart rates on QTd and to compare the effect of different methods of stress induction in patients with varying degrees of CAD when estimating QTd.We studied 58 patients, 22 with prior myocardial infarction (MI), 25 without MI or wall motion disturbances at rest, and 11 patients without evidence of CAD. Prior to coronary angiography, standard 12-lead ECGs were obtained at rest as well as during dynamic exercise and pharmacologic stress using arbutamine simultaneously with echocardiography. QTd was determined at each stress level by subtracting minimal from maximal QT interval duration.QTd values at rest were not consistently higher in the patients with CAD. At maximal heart rate, QTd was statistically significantly higher in patients with CAD with a better discrimination between groups for pharmacologic stress (p < 0.005 for exercise, p < 0.0001 for arbutamine). Patients after MI had higher QTd values under all conditions than did the groups without MI. As in patients with CAD, the values of this group changed more radically as a result of pharmacologic stress.Patients with CAD can be identified on the basis of QTd under stress. These changes were not as marked in patients with MI as their rest values were already increased. Overall, drug-induced stress produced greater differences than dynamic exercise, suggesting that the ischemic threshold might be lower in the former.

Pharmacological stress testing may be used in the diagnosis of coronary artery disease when there are contra-indications to the use of conventional exercise protocols. The responses to such testing using arbutamine and to conventional treadmill exercise were compared in eight patients. Respiratory gas analysis and cardiovascular observations were performed during both tests. For an equivalent increment in heart rate, both protocols increased systolic blood pressure and serum lactate. Minute ventilation and oxygen consumption also rose during both protocols, but much more so with exercise. The end-tidal partial pressure of CO(2) [35.1 (S.D. 3. 1) to 30.8 (6.6) mmHg] and the dead space/tidal volume ratio (V(D)/V(T)) [0.37 (0.09) to 0.33 (0.08)] fell significantly during arbutamine infusion, but the respiratory exchange ratio did not change during either protocol. Oxygen pulse, a marker of stroke volume, did not change significantly after arbutamine, but rose markedly after exercise [arbutamine, 3.9 (1.1) to 3.37 (0.7) ml. min(-1).beat(-1); exercise, 4.7 (1.4) to 16.1 (4.6) ml.min(-1). beat(-1) (P<0.0001 compared with baseline); difference between peak responses: P<0.0001]. We conclude that arbutamine simulates some of the physiological responses to exercise, although a number of these responses are less marked than during conventional exercise, in particular cardiac output (oxygen pulse). An increase in ventilation is produced, possibly due to direct stimulation of arterial chemoreceptors. These data suggest that the main action of arbutamine is to increase central drive rather than to establish peripheral demand.

Pharmacological stress in conjunction with radionuclide myocardial perfusion imaging has become a widely used noninvasive method of assessing patients with known or suspected coronary artery disease. In the United States, over one third of perfusion imaging studies are performed with pharmacological stress. Pharmacological stress agents fall into two categories: coronary vasodilating agents such as dipyridamole and adenosine, and cardiac positive inotropic agents such as dobutamine and arbutamine. For both, in the presence of coronary artery disease (CAD), perfusion image abnormalities result from heterogeneity of coronary blood flow reserve. Vasodilating agents work directly on the coronary vessels to increase blood flow, whereas inotropic agents work indirectly by increasing myocardial work load, which then leads to an increase in coronary blood flow. Both classes of agents have high accuracies for diagnosing coronary artery disease, and they have excellent safety records with acceptably low occurrences of side effects. For dipyridamole planar thallium imaging, pooled analysis yields a sensitivity of 85% and a specificity of 87% for diagnosis of coronary disease, but there is a large variation in reported values depending on various factors, such as the extent of postcatheterization referral bias, the type of imaging (planar versus single photon emission computed tomography [SPECT]), the types of patients being studied (single versus multivessel disease, men versus women), and the imaging agent used (thallium versus one of the technetium-based agents). Diagnostic accuracies for adenosine are similar to those of dipyridamole, with reported overall sensitivities ranging from 83% to 97%, and specificities ranging from 38% to 94%. For dobutamine, pooled analyses yield a sensitivity of 82% and a specificity of 75%. There is some concern that dobutamine may interfere with uptake of technetium-99m sestamibi, lowering the sensitivity for detection of disease, and thus the vasdodilating agents are generally preferred. Pharmacological stress testing has high clinical use for risk stratifying patients with known or suspected CAD, in patients after myocardial infarction, and in patients needing noncardiac surgery. Vasodilating agents are particularly advantageous in assessing post-myocardial infarction patients, allowing testing as soon as 2 days after the event. Like patients undergoing exercise stress testing, patients with normal perfusion images by pharmacological stress have a <1% annual incidence of cardiac events. The likelihood of an event increases with the extent and severity of perfusion abnormalities. However, it is important to consider clinical variables when using perfusion imaging for risk stratification, particularly in the presurgery patients. As with exercise testing, adjunct markers such as ST segment depression during testing, lung uptake of radiotracer (if thallium is used), and ventricular cavity dilatation add additional prognostic information to that available from the perfusion images alone. The aim of current research is to find better agents that are easier to use and that have fewer side effects. MRE-0470 is an experimental vasodilating agent that is more receptor selective than adenosine and promises a lower incidence of hypotension. Arbutamine more closely simulates exercise than dobutamine, and it can be administered by a closed-loop computerized delivery device. Work is also underway to look at novel uses of pharmacological stress agents, such as acquiring gated SPECT images during dobutamine infusion to enhance detection of myocardial viability. With increasing use of noninvasive testing in elderly patients and in patients with comorbidities that preclude adequate exercise, pharmacological stress testing has become an indispensable tool for radionuclide myocardial perfusion imaging studies. A good understanding of pharmacological stress testing is essential for performing high-quality nuclear cardiology