Regadenoson Stress Research Articles

Age and Gender as Predictors of Benefit From Aminophylline Administration in Patients Undergoing Regadenoson Stress Myocardial Perfusion Imaging

Regadenoson is a selective adenosine A2A-receptor agonist, used as a pharmacological stress agent for myocardial perfusion imaging. It is associated with frequent adverse effects (AEs), particularly among individuals younger than 65 years of age and women. Intravenous aminophylline administration following regadenoson, as described in the ASSUAGE trial, reduces the incidence of AE. In this substudy of the ASSUAGE trial, we compared the absolute and relative benefits of aminophylline administration versus placebo, between subgroups of age (<65 vs. ≥65 years) and gender (women vs. men). Study endpoints were headache, gastrointestinal AE, any regadenoson AE, and tolerability (feeling comfortable during regadenoson stress). Among patients <65years, compared with ≥65 years, aminophylline administration was associated with greater absolute risk reduction (ARR) in gastrointestinal AE (16% vs. 5%, P = 0.01) and any regadenoson AE (31% vs. 12%, P = 0.001), and with a greater absolute improvement in tolerability (21% vs. 1%, P < 0.001). Men received greater ARR in gastrointestinal AE than women (18% vs. 2%, P < 0.001). There was no difference in the ARR in other AE between subgroups. Across all subgroups, aminophylline use was associated with a consistent trend toward relative reduction in AE rates and improved tolerability. No significant interaction was identified between subgroups and aminophylline administration in reducing AE. In conclusion, although aminophylline use was associated with greater ARR in AE in certain subgroups, a consistent benefit with aminophylline administration was attained in all subgroups. Thus, to predictably reduce regadenoson AE and improve tolerability, aminophylline should be administered routinely to all patients as per the ASSUAGE protocol.

Coronary Angiographic Significance of Hyperacute St-T Changes Associated with Regadenoson Stress

An abnormal electrocardiographic stress test is typically characterized by ST segment depression. In rare cases, ST segment elevation is observed, which, in the absence of diagnostic Q waves, has anatomic specificity for localized myocardial ischemia. Most instances of ST elevation occurring during cardiac stress testing have been observed with exercise, with only six cases reported with pharmacologic stress. Despite different physiologic mechanisms for inducing myocardial ischemia, development of ST segment elevation during pharmacologic stress, as illustrated by the present case, may also be indicative of critical coronary stenoses, warranting urgent coronary arteriography.

Comparison of hemodynamic and stress testing variables in patients undergoing regadenoson stress myocardial perfusion imaging to regadenoson with adjunctive low-level exercise myocardial perfusion imaging

Regadenoson (REG), a selective adenosine A2a receptor agonist, is becoming the preferred pharmacologic agent for stress myocardial perfusion imaging (MPI). Hemodynamic and stress variables, immediate safety and use of aminophylline when using REG combined with low-level exercise (REG WALK MPI) compared with REG MPI, have not been well studied and formed the basis of our study. Retrospective evaluation of patients who underwent REG MPI (n = 887) was compared to patients undergoing REG WALK MPI (n = 485) from January to November 2009. Patient demographics, hemodynamic parameters, REG MPI data, side effects, immediate major clinical events, and use of aminophylline were evaluated. Patients in REG WALK MPI group tended to be younger, male and obese compared to patients in REG MPI group. REG WALK MPI patients had higher stress heart rate (103 ± 20.5 vs 84 ± 19 bpm, P = .001), higher heart rate reserve (36.3 ± 19 vs 14.7 ± 15.5 bpm, P < .001), and greater systolic blood pressure rise (4.8 ± 21.3 vs -8.9 ± 19.8 mm Hg, P < .001), compared to REG MPI patients. No major adverse events were reported immediately after REG WALK MPI. There were no differences in drug-related side effects in between the two groups; however, the use of aminophylline was lower in REG WALK MPI Group (5.6% vs 11.4%, P = .001). REG WALK MPI gives more favorable hemodynamic response with lesser use of aminophylline and no increase in adverse events when compared with REG MPI.

Regadenoson induced acute ST-segment elevation myocardial infarction and multivessel coronary thrombosis

A 41-year-old man with ischemic cardiomyopathy presented for regadenoson stress test with myocardial perfusion imaging (MPI). He had prior myocardial infarction (MI), a left anterior descending coronary artery (LAD) stent, and an implantable cardioverterdefibrillator (ICD). His baseline left ventricular systolic ejection fraction was 21%. He was on aspirin, carvedilol, lisinopril, lovastatin and clopidogrel. The MPI at rest demonstrated a large apical perfusion defect of the left ventricle (Figure 1). His pre- and post-stress test blood pressures were 120/79 and 129/90 mm Hg, and pre- and post-stress test heart rates were 75 and 114 bpm. The patient was asymptomatic, and thus did not receive aminophylline reversal after the stress test. About 15 minutes after the injection of regadenoson, he developed severe chest pain and acute ST-segment elevation in leads II, III, aVF, V4, V5 and V6 on the electrocardiogram (ECG), consistent with acute MI (Figure 2). The patient then had unstable ventricular tachycardia which was terminated by his ICD. He received sublingual nitroglycerine when the blood pressure was stable, plus intravenous heparin and saline while being promptly transported to the cardiac catheterization laboratory. An emergent coronary angiography revealed acute thrombosis and vessel occlusion of 99‐ 100% in the proximal LAD and mid right coronary artery (RCA) (Figure 3). Export thrombectomy was performed first, then bare metal stents were implanted to the LAD and RCA with 0% residual stenosis (Figure 4). His troponin I peaked at 62.7 ng/dL. He recovered fully and was discharged home 4 days later.

096 REGADENOSON IN EUROPE: FIRST- YEAR EXPERIENCE OF REGADENOSON STRESS COMBINED WITH SUBMAXIMAL EXERCISE IN PATIENTS UNDERGOING MPS

Background Regadenoson is a selective A2a specific adenosine receptor agonists. It has been developed to avoid side effects associated with common pharmacological stress agents. European approval was granted by the EMA in 2010. The aim of this study was to assess the side effect profile of regadenoson and to compare this experience with other forms of stress used over the same period. Methods Since July 2011 we prospectively studied 1764 consecutive patients referred for MPS. All clinical, stress and imaging data have been recorded and analysed using the Excel Data Analysis Toolpak and SPSS. Symptoms during stress were recorded and defined as mild, moderate or severe. An adverse event was defined as any symptom that persisted for more than 30 min or that required investigation or treatment. Adenosin, dobutamine and dynamic exercise were administered and done according to Royal Brompton Patient Group Direction (PGD). Regadenoson was given as a 400 µg bolus intravenously over 10–30 s followed by a saline flush over 10 s and then the radiopharmaceutical. Results 130 patients underwent adenosine stress, 1581 regadenoson stress, 39 dobutamine stress and 14 dynamic exercise stress. Symptoms were common with all forms of pharmacological stress occurring in 75% with adenosine, 63% with regadenoson and 46% with dobutamine. Chest discomfort and flushing occurred more commonly with adenosine (29% and 25% respectively) than with regadenoson (12% and 7%), but light headedness more common with regadenoson (7%) than with adenosine (1%). Twelve patients with regadenoson (1%) had diarrhoea compared with none with adenosine. The severity of symptoms did not differ between agents being mild, moderate and severe 84.1%, 14% and 1.9% with adenosine, 88.1%, 10.1%, 1.7% respectively with regadenoson and 82.4%, 17.7%, 0% with dobutamine. Eight patients had adverse events, all with regadenoson, although the difference was not statistically significant (p=0.818). Three events were moderate and two severe, the latter with sinus arrest and asystole lasting 30 s and 10 s and requiring CPR. All patients recovered fully without sequelae or admission to hospital. No patient developed bronchospasm with regadenoson with the exception of a single patient without known airways disease who developed mild bronchospasm that responded to salbutamol inhaler. Conclusions We have studied 1764 stress tests for MPS over a 12-month period in order to assess the symptom profile of regadenoson in the largest European cohort to date. Regadenoson combined with exercise is well tolerated, notably also in patients with asthma/COPD. The majority of adverse events were vaso-vagal episodes without sequelae. There is no clear direct mechanism by which regadenoson might cause vaso-vagal syncope.

Safety and feasibility of adjunctive regadenoson injection at peak exercise during exercise myocardial perfusion imaging: The Both Exercise and Regadenoson Stress Test (BERST) trial

BackgroundThe data existing in the literature regarding the safety of using regadenoson with symptom-limited exercise are limited, which motivated the authors to undertake this randomized study. MethodsWe offered patients scheduled to undergo vasodilator stress nuclear myocardial perfusion imaging the opportunity to exercise instead. Patients who failed to reach target heart rate (THR) were randomized to (1) receive regadenoson at peak exercise or (2) stop exercise and receive regadenoson at rest. Patients who reached THR received a standard Tc-99m sestamibi injection with no regadenoson. Results200 patients were included (66% male, mean age 52.5 ± 13.6). 125 patients (62%) reached THR with exercise alone. All stress protocols were well tolerated, and there were no significant adverse events. There were no statistically significant differences in the extent of perfusion abnormalities, image quality, or rate of referral to cardiac catheterization within 60 days between the groups. In fully adjusted logistic regression models, beta-blocker use and diabetes remained significant univariate predictors of failure to reach THR (OR 0.21, 95% CI 0.1-0.5, P < .0001, OR 0.34, 95% CI 0.2-0.7, P = .004, respectively). ConclusionsA protocol combining regadenoson at peak exercise in patients unable to reach THR with exercise is feasible, well-tolerated, and yields comparable imaging results to a standard regadenoson injection at rest. In addition, pharmacologic stress testing may be over-ordered in current clinical practice, as patients referred for such testing were often able to exercise.

Myocardial Perfusion: Near-automated Evaluation from Contrast-enhanced MR Images Obtained at Rest and during Vasodilator Stress

To develop and validate a technique for near-automated definition of myocardial regions of interest suitable for perfusion evaluation during vasodilator stress cardiac magnetic resonance (MR) imaging. The institutional review board approved the study protocol, and all patients provided informed consent. Image noise density distribution was used as a basis for endocardial and epicardial border detection combined with nonrigid registration. This method was tested in 42 patients undergoing contrast material-enhanced cardiac MR imaging (at 1.5 T) at rest and during vasodilator (adenosine or regadenoson) stress, including 15 subjects with normal myocardial perfusion and 27 patients referred for coronary angiography. Contrast enhancement-time curves were near-automatically generated and were used to calculate perfusion indexes. The results were compared with results of conventional manual analysis, using quantitative coronary angiography results as a reference for stenosis greater than 50%. Statistical analyses included the Student t test, linear regression, Bland-Altman analysis, and κ statistics. Analysis of one sequence required less than 1 minute and resulted in high-quality contrast enhancement curves both at rest and stress (mean signal-to-noise ratios, 17±7 [standard deviation] and 22±8, respectively), showing expected patterns of first-pass perfusion. Perfusion indexes accurately depicted stress-induced hyperemia (increased upslope, from 6.7 sec(-1)±2.3 to 15.6 sec(-1)±5.9; P<.0001). Measured segmental pixel intensities correlated highly with results of manual analysis (r=0.95). The derived perfusion indexes also correlated highly with (r up to 0.94) and showed the same diagnostic accuracy as manual analysis (area under the receiver operating characteristic curve, up to 0.72 vs 0.73). Despite the dynamic nature of contrast-enhanced image sequences and respiratory motion, fast near-automated detection of myocardial segments and accurate quantification of tissue contrast is feasible at rest and during vasodilator stress. This technique, shown to be as accurate as conventional manual analysis, allows detection of stress-induced perfusion abnormalities.

Coronary vasospasm during a regadenoson stress test

A 43 year-old male was referred for pharmacological stress testing in 2010 in the setting of increasing dyspnea on exertion and atypical chest pain. He had been diagnosed with hypertrophic cardiomyopathy following a ventricular fibrillation arrest in 2004. At that time, he underwent a negative evaluation for coronary atherosclerosis and intracardiac defibrillator implantation, and had done well since. Upon regadenoson injection (0.4 mg over 10 s) he became tachycardic, diaphoretic, and complained of severe chest tightness. His ECG showed exaggeration of baseline abnormalities, non-specific for ischemia (Figs. 1, 2). He was given aminophylline (150 mg intravenous) with resolution of his symptoms. Myocardial imaging revealed a moderate to large-sized reversible defect involving the anteroseptal, anterior, and inferolateral walls, as well as stress-associated left ventricular dilation (Fig. 3). Subsequent coronary angiography was negative for significant coronary artery disease or anatomical coronary anomalies (Fig. 4). Adenosine and its analogs provoke coronary vasodilation via activation of A2A type adenosine receptors, and are useful as pharmacological stress agents by exploiting flow-reserve differences between normal and atherosclerotic coronary artery segments [1]. However, coronary vasospasm is a well-known occurrence of adenosine administration, and milder side effects are frequently encountered, likely related to the activation of non-A2A type receptors [2].

Quantitative Three-Dimensional Evaluation of Myocardial Perfusion During Regadenoson Stress Using Multidetector Computed Tomography

The ability of multidetector computed tomography (MDCT) to detect stress-induced myocardial perfusion abnormalities is of great clinical interest as a potential tool for the combined evaluation of coronary stenosis and its hemodynamic significance. We tested the hypothesis that quantitative 3-dimensional (3D) analysis of myocardial perfusion from MDCT images obtained during regadenoson stress would more accurately detect the presence of significant coronary artery disease (CAD) than identical analysis when performed on resting MDCT images. We prospectively studied 50 consecutive patients referred for CT coronary angiography (CTCA) who agreed to undergo additional imaging with regadenoson (0.4 mg; Astellas). Images were acquired using prospective gating (256-channel; Philips). Custom analysis software was used to define 3D myocardial segments, and calculate for each segment an index of severity and extent of perfusion abnormality, Qh, which was compared with perfusion defects predicted by the presence and severity of coronary stenosis on CTCA. Three patients were excluded because of image artifacts. In the remaining 47 patients, CTCA depicted stenosis more than 50% in 23 patients in 37 of 141 coronary arteries. In segments supplied by the obstructed arteries, myocardial attenuation was slightly reduced compared with normally perfused segments at rest (mean [SD], 91 [21] vs 93 [26] Hounsfield units, not significant) and, to a larger extent, at peak stress (102 [21] vs 112 [20] Hounsfield units, P < 0.05). In contrast, index Qh was significantly increased at rest (0.40 [0.48] vs 0.26 [0.41], P < 0.05) and reached a nearly 3-fold difference at peak stress (0.66 [0.74] vs 0.28 [0.51], P < 0.05). The addition of regadenoson improved the diagnosis of CAD, as reflected by an increase in sensitivity (from 0.57 to 0.91) and improvement in accuracy (from 0.65 to 0.77). Quantitative 3D analysis of MDCT images allows objective detection of CAD, the accuracy of which is improved by regadenoson stress.

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson.

BackgroundAdenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) – more specifically, whether regadenoson stress imaging should be performed before or after rest imaging.MethodsTwenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov).ResultsIn all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia.ConclusionsMPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study.Trial registrationClinicalTrials.gov NCT00871260

Rapid Detection of Coronary Artery Stenoses With Real-Time Perfusion Echocardiography During Regadenoson Stress

Real-time myocardial contrast echocardiography permits the detection of myocardial perfusion abnormalities during stress echocardiography, which may improve the accuracy of the test in detecting coronary artery stenoses. We hypothesized that this technique could be used after a bolus injection of the selective A2A receptor agonist regadenoson to rapidly and safely detect coronary artery stenoses. In 100 patients referred for quantitative coronary angiography, real-time myocardial contrast echocardiography was performed during a continuous intravenous infusion of 3% Definity at baseline and at 2-minute intervals for up to 6 minutes after a regadenoson bolus injection (400 μg). Myocardial perfusion was assessed by examination of myocardial contrast replenishment after brief high mechanical index impulses. A perfusion defect was defined as a delay (>2 seconds) in myocardial contrast replenishment in 2 contiguous segments. Wall motion was also analyzed. The overall sensitivity/specificity/accuracy for myocardial perfusion analysis in detecting a >50% diameter stenosis was 80%/74%/78%, whereas for wall motion analysis it was 60%/72%/66% (P<0.001 for differences in sensitivity). Sensitivity for myocardial perfusion analysis was highest on images obtained during the first 2 minutes after regadenoson bolus (P<0.001 compared with wall motion), whereas wall motion sensitivity was highest at the 4-to-6-minute period after the bolus. No significant side effects occurred after regadenoson bolus injection. Regadenoson real-time myocardial contrast echocardiography appears to be a feasible, safe, and rapid noninvasive method for the detection of significant coronary artery stenoses.

Regadenoson Stress SPECT MPI for Prediction of Outcomes in Patients with Impaired Left Ventricular Function: A Comparison with Adenosine Stress

There is no information on the performance of the new A2a receptor agonist stressor Regadenoson in predicting outcomes in patients with decreased LV systolic function. Furthermore, no prognostic comparison data with other stressor agents have been reported. The purpose of this study was to evaluate the prognostic power of Regadenoson in patients with decreased LV function and to compare with Adenosine.

Detection of myocardial perfusion abnormalities using ultra-low radiation dose regadenoson stress multidetector computed tomography

The ability of multidetector computed tomography (MDCT) to detect stress-induced myocardial perfusion abnormalities is of great clinical interest as a potential tool for the combined evaluation of coronary stenosis and its significance. However, stress testing requires repeated scanning that is associated with additional radiation exposure and iodine contrast. Our goal was to determine the effects of reduced tube voltage and contrast dose on the ability to detect perfusion abnormalities. We studied 40 patients referred for coronary CT angiography (CTA) who agreed to undergo additional imaging after administration of an A(2A)-agonist (regadenoson 0.4 mg). Images were acquired at rest and during hyperemia with prospective gating with 120 kV tube voltage with 80-90 mL of contrast in 20 patients (group 1) and 100 kV with 55-70 mL of contrast in the remaining 20patients (group 2). Custom 3D analysis software was used to define 3D myocardial segments and measure x-ray attenuation in each segment. In each group of patients, myocardial attenuation was averaged for segments supplied by coronary arteries with stenosis causing >50% luminal narrowing on coronary CTA and separately for segments supplied by arteries without significant stenosis. Coronary CTA detected stenosis >50% in 23 of 120 coronary arteries in 16 of 40 patients. In all patients combined, myocardial attenuation increased from 86 ± 9 at rest to 110 ± 17 HU with stress, reflecting an increase in tissue blood flow, despite the decrease in left ventricular cavity attenuation (347 ± 72 to 281 ± 55 HU), reflecting an increase in cardiac output. Importantly, in both groups, myocardial attenuation was equally reduced in segments supplied by diseased arteries (group 1: 119 ± 19 vs 103 ± 14 HU, P < 0.05; group 2: 108 ± 20 vs 97 ± 16 HU, P < 0.05), despite the 74% reduction in radiation (from 7.4 ± 2.8 to 1.9 ± 0.45 mSv) and the 28% reduction in contrast dose (from 84 ± 7 to 60 ±7 mL) (both P < 0.05). Regadenoson stress MDCT imaging can detect hypoperfused myocardium even when imaging settings are optimized to provide a significant reduction in radiation and contrast doses.

Optimal timing of rest perfusion with regadenoson stress testing - normal volunteer study of quantitative MRI perfusion

Many MRI perfusion protocols perform rest imaging a few minutes after stress imaging. Regadenoson is a new, selective Adenosine-2A receptor agonist used for myocardial perfusion imaging. The purpose of this study was to assess how well rest perfusion imaging 20 minutes after regadenoson stress reflects true baseline rest perfusion.

Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: Rationale and design of a prospective, randomized, multicenter study

BackgroundCaffeine attenuates the coronary hyperemic response to adenosine by competitive A2A receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A2A agonist. MethodsThis multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. ConclusionThe results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

Safety of regadenoson in patients with end-stage liver disease

BackgroundRegadenoson is a selective A2A receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined. Methods and ResultsWe studied 168 consecutive patients with ESLD who had regadenoson stress gated single photon emission computed tomography MPI between January 2008 and March 2010 before planned orthotopic liver transplantation and compared the hemodynamic responses and safety profile to 168 control patients. There were 72 women (43%) in ESLD versus 87 (52%) in the control group (P= .1). The patients with ESLD were younger (58 ± 7 vs 62 ± 12 years, P= .0002), but more likely to be Caucasians (P= .002). The MPI images were normal in 161 patients (96%) in each group. The left ventricular ejection fraction was 72 ± 10% in ESLD and 66 ± 11% in the control patients (P= .0001). The heart rate increase in response to regadenoson was lower in patients with ESLD than in the control group (16 ± 11 vs 23 ± 16 bpm, P= .0001), but the changes in systolic and diastolic blood pressures were similar (−9 ± 12 vs −11 ± 14 mmHg and −6 ± 8 vs −7 ± 10 mmHg, respectively, P= NS). There were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study. ConclusionThis is the first study to document the tolerability and safety profile of regadenoson in patients with ESLD.

Advances in Pharmacologic Stress Agents: Focus on Regadenoson

Myocardial perfusion imaging using radionuclides is a well-established protocol for determining the diagnosis, prognosis, and management of coronary artery disease. Pharmacologic stress agents are used to induce cardiac hyperemia in patients unable to achieve the target workload by physical exercise alone. The vasodilators adenosine and dipyridamole are most commonly used, with dobutamine used only when these agents are contraindicated. However, because of frequent and intense side effects, as well as complex procedures both for patients and the nuclear medicine staff, there is room for improvement in these traditional stress agents. An ideal stress agent would be effective, safe, and well tolerated; have a simple protocol; be suitable for use in patients with reactive airway disease; and have few restrictions for the patient to adhere to before the procedure. Neither adenosine nor dipyridamole are receptor-specific, and act on A(1), A(2A), A(2B), and A(3) adenosine receptors. As it is the A(2A) receptor that mediates the desired coronary vasodilation, the A(1), A(2B), and A(3) adenosine receptors are deemed responsible for most side effects associated with adenosine and dipyridamole. A(2A)-selective pharmacologic stress agents should mediate the required hyperemic response while reducing the frequency of adverse events. The only selective A(2A) adenosine receptor agonist currently approved for clinical use as a pharmacologic stress agent for myocardial perfusion imaging is regadenoson. Regadenoson has demonstrated non-inferiority to adenosine for detecting reversible myocardial perfusion defects in phase 3 trials, and patients were more comfortable during the regadenoson stress procedure than during an adenosine infusion. As regadenoson dosing is not dependent on patient weight or renal impairment and can be administered by rapid injection, it has the potential to simplify the stress procedure, reduce costs, and streamline the working day for the staff of the nuclear medicine department. In this review, the need to improve on older pharmacologic stress agents will be considered, along with an assessment of how A(2A) receptor agonists fulfill that potential. Practical aspects of regadenoson are reviewed, and the impact that A(2A) receptor agonist use may have on the nuclear medicine department is evaluated.

Lessons from regadenoson and low-level treadmill/regadenoson myocardial perfusion imaging: Initial clinical experience in 1263 patients

BackgroundRegadenoson is a pharmacologic stress agent, which was recently approved for stress myocardial perfusion imaging (MPI). Aside from the initial protocol-driven studies, clinical experience with this stress agent is limited. Furthermore, low-level treadmill testing in a large population with regadenoson has not previously been evaluated. We describe our experience in the first 6 months of routine inpatient and outpatient clinical use. MethodsBetween 7/1/08 and 12/04/08, 1263 patients underwent regadenoson stress testing (596 with low-level treadmill, 667 supine). Past medical history, clinical symptoms during stress, and changes in systolic blood pressure were prospectively recorded. ResultsLow-level treadmill testing was well tolerated in our patient population. Shortness of breath, dizziness, palpitations, transient heart block, and nausea were less frequent when patients were able to exercise. In our population, 51% experienced a drop in systolic blood pressure greater than 10 mmHg, with 9% experiencing a decrease in more than 30 mmHg. This decrease in blood pressure was more common in patients who underwent low-level treadmill testing vs those that were supine (56% vs 47%, P-value < 0.001). The frequency of symptoms in our entire population was as follows: chest pain 35%, dizziness/lightheadedness 16%, shortness of breath 27%, headache 1.4%, nausea 2.3%, and palpitations 5%. There were no major hemodynamic or conduction abnormalities. In the 16% of patients, a history of COPD/Asthma Regadenoson MPI was well tolerated. There were no procedural deaths. ConclusionRegadenoson and Regadenoson combined with low level exercise MPI appear to be safe and well tolerated. An asymptomatic fall in systolic blood pressure seems to be more common in patients who undergo low-level treadmill testing.

Safety of Regadenoson in Patients with End-Stage Renal Disease

Regadenoson is a selective A(2A) receptor agonist that was recently approved by the Food and Drug Administration for vasodilator stress myocardial perfusion imaging. Because the drug is cleared by renal excretion, its safety in patients with end-stage renal disease (ESRD) needs to be determined. We studied 277 consecutive patients with ESRD who had undergone regadenoson stress gated single photon emission computed tomography myocardial perfusion imaging and compared their side effect profile and safety outcome to those of 134 patients with normal kidney function. The ESRD group included 164 men (59%) and the control group included 73 men (54%; p = NS). The patients with ESRD were younger than the controls (52 +/- 11 years vs 61 +/- 12 years; p <0.001). The myocardial perfusion imaging findings were abnormal in 53 patients (19%) with ESRD and in 24 patients in the control group (18%; p = NS). The left ventricular ejection fraction was 57 +/- 12% in the ESRD group and 64 +/- 12% in the control group (p <0.001). The changes in heart rate and systolic blood pressure (from baseline to peak stress) were 20 +/- 12 beats/min versus 22 +/- 13 beats/min and -11 +/- 24 mm Hg versus -12 +/- 23 mm Hg in the ESRD and control groups, respectively (p = NS for both). Very few patients in either group reported symptoms during the stress test. No medication-related hospitalizations, serious events, or death occurred in either group within 30 days of the study. In conclusion, this is the first study to document the safety of regadenoson in a large number of patients with ESRD. The drug was well tolerated, and the hemodynamic and side effect profiles were similar to those of patients with normal renal function.

Effects of Adenosine and a Selective A2A Adenosine Receptor Agonist on Hemodynamic and Thallium-201 and Technetium-99m–SestaMIBI Biodistribution and Kinetics

The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics. The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics. Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting. The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p < 0.01; adenosine: 2.7 +/- 0.04 min, p < 0.01) for both vasodilator stressors. The relative microsphere flow deficit (0.34 +/- 0.02%) during regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p < 0.001) or (201)Tl (0.53 +/- 0.02%, p < 0.001), although (201)Tl tracked the flow deficit within the ischemic region better than (99m)Tc-sestaMIBI. The perfusion defect score was larger with (201)Tl (22 +/- 2.8% left ventricular) than with (99m)Tc-sestaMIBI (17 +/- 1.7% left ventricular, p < 0.05) on ex vivo single-photon emission computed tomography images. The bolus administration of regadenoson produced a hyperemic response comparable to a standard infusion of adenosine. The biodistribution and clearance of both (201)Tl and (99m)Tc-sestaMIBI during regadenoson were similar to adenosine vasodilation. Ex vivo perfusion images under the most ideal conditions permitted detection of a critical stenosis, although (201)Tl offered significant advantages over (99m)Tc-sestaMIBI for perfusion imaging during regadenoson vasodilator stress.