Hemiplegic migraine episode triggered by regadenoson.

SPECT and PET myocardial perfusion imaging (MPI) are widely used to evaluate patients for coronary artery disease. Regadenoson (a selective A2A adenosine receptor agonist) is a commonly used vasodilator agent for stress MPI because of its safety profile and ease of use. Common adverse reactions such as headache, shortness of breath, flushing, and chest and abdominal discomfort are typically mild and can be effectively reversed using methylxanthines such as aminophylline and caffeine. Neurological adverse reactions such as seizure and stroke have rarely been reported with the use of regadenoson. The hemodynamic changes associated with regadenoson administration, such as an exaggerated hypotensive or hypertensive response, may be the cause for the reported cerebrovascular accidents. Activation of central nervous system A2A adenosine receptors is thought to be responsible for seizure episodes in patients with or without known histories of seizure. A2A adenosine receptors activation is also believed to play a role in headaches and migraine. This patient reported who has a history of hemiplegic migraine developed left side weakness and headache following the administration of regadenoson during a PET MPI study. Imaging work-up to rule out cerebrovascular accident was normal. After 1 hour from the onset of his symptoms, his weakness and headache significantly improved with complete resolution within 24 hours. We concluded that regadenoson triggered a hemiplegic migraine episode in this patient, which has not been previously reported in the literature. It may be prudent to avoid regadenoson and adenosine use in patients with a history of hemiplegic migraine.

The A2A receptor agonist CGS 21680 has beneficial and adverse effects on disease development in a humanised mouse model of graft-versus-host disease.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative method for blood cancers and other blood disorders, but is limited by the development of graft-versus-host disease (GVHD). GVHD results in inflammatory damage to the host liver, gastrointestinal tract and skin, resulting in high rates of morbidity and mortality in HSCT recipients. Activation of the A2A receptor has been previously demonstrated to reduce disease in allogeneic mouse models of GVHD. This study aimed to investigate the effect of A2A activation on disease development in a humanised mouse model of GVHD. Immunodeficient non-obese diabetic-severe combined immunodeficiency-interleukin (IL)-2 receptor γnull (NSG) mice injected with human (h) peripheral blood mononuclear cells (hPBMCs), were treated with either the A2A agonist CGS 21680 or control vehicle. Contrary to the beneficial effect of A2A activation in allogeneic mouse models, CGS 21680 increased weight loss, and failed to reduce the clinical score or increase survival in this humanised mouse model of GVHD. Moreover, CGS 21680 reduced T regulatory cells and increased serum human IL-6 concentrations. Conversely, CGS 21680 reduced serum human tumour necrosis factor (TNF)-α concentrations and leukocyte infiltration into the liver, indicating that A2A activation can, in part, reduce molecular and histological GVHD in this model. Notably, CGS 21680 also prevented healthy weight gain in NSG mice not engrafted with hPBMCs suggesting that this compound may be suppressing appetite or metabolism. Therefore, the potential benefits of A2A activation in reducing GVHD in HSCT recipients may be limited and confounded by adverse impacts on weight, decreased T regulatory cell frequency and increased IL-6 production.

Therapeutic potential of A2 adenosine receptor pharmacological regulators in the treatment of cardiovascular diseases, recent progress, and prospective.

Adenosine and its analogs are of particular interest as potential therapeutic agents for treatment of cardiovascular diseases (CVDs). A2 adenosine receptor subtypes (A2a and A2b) are extensively expressed in cardiovascular system, and modulation of these receptors using A2 adenosine receptor agonists or antagonists regulates heart rate, blood pressure, heart rate variability, and cardiovascular toxicity during both normoxia and hypoxia conditions. Regulation of A2 adenosine receptor signaling via specific and novel pharmacological regulators is a potentially novel therapeutic approach for a better understanding and hence a better management of CVDs. This review summarizes the role of pharmacological A2 adenosine receptor regulators in the pathogenesis of CVDs.

Myocardial Stress Perfusion MRI: Experience in Pediatric and Young-Adult Patients Following Arterial Switch Operation Utilizing Regadenoson.

Dextro-transposition of the great arteries (D-TGA) is one of the most common cyanotic heart lesions. The arterial switch operation (ASO) is the preferred surgical palliation for D-TGA. One of the primary concerns following the ASO is complications arising from the coronary artery transfer. There is a need for myocardial perfusion assessment within ASO patients. There is no report on the utility of regadenoson as a stress agent in children following ASO. Our objective was to observe the safety and feasibility of regadenoson as a pharmacologic stressor for perfusion cardiac MR in a pilot cohort of pediatric and young-adult patients who have undergone ASO. We reviewed our initial experience with regadenoson stress cardiac MR in 36 pediatric and young-adult patients 15.1 ± 4.5 years (range 0.2-22 years) with history of ASO. The weight was 61.6 ± 21.5 kg (range 3.8-93 kg). All patients underwent cardiac MR because of concern for ischemia. Subjects' heart rate and blood pressure were monitored and pharmacologic stress was induced by injection of regadenoson. We evaluated their hemodynamic response and adverse effects using changes in vital signs and onset of symptoms. A pediatric cardiologist and radiologist qualitatively assessed myocardial perfusion and viability images. All stress cardiac MR examinations were completed without adverse events. Resting heart rate was 72 ± 13 beats per minute (bpm) and rose to peak of 120 ± 17 bpm (95 ± 50% increase, p < 0.005) with regadenoson. Image quality was considered good or diagnostic in all cases. A total of 11/36 (31%) patients had a perfusion defect on the stress FPP images. 14 of the 36 patients (39%) underwent cardiac catheterization within 6 months of the CMR and the findings showed excellent agreement. Regadenoson may be a useful coronary hyperemia agent to utilize for pediatric patients following arterial switch procedure when there is concern for ischemia. The ability to administer as a single bolus with one IV makes it advantageous in pediatrics. In a limited number of cases, regadenoson stress perfusion showed excellent agreement with cardiac catheterization.

Safety of regadenoson stress testing in patients with pulmonary hypertension.

OBJECTIVES: We sought to determine the safety of regadenoson stress testing in patients with PH. BACKGROUND: PH is increasingly recognized at more advanced ages. As many as one-third of patients with PH have coronary artery disease. Because of their physical limitations, patients with PH are unable to adequately exercise. Regadenoson can potentially have an adverse impact due to their tenuous hemodynamics. Current guidelines suggest performing a coronary angiography in patients with PH who have angina or multiple coronary risk factors. METHODS: We identified 67 consecutive patients with confirmed PH by catheterization (mean PA > 25 mmHg not due to left heart disease) who underwent MPI with regadenoson stress. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson. RESULTS: No serious events occurred. Common side effects related to regadenoson were observed, dyspnea being the most common (70.6%). No syncope occurred. Heart rate increased from 74.6 ± 14 to 96.3 ± 18.3 bpm, systolic blood pressure increased from 129.8 ± 20.9 to 131.8 ± 31 mmHg, and diastolic blood pressure decreased from 77.1 ± 11.4 to 72.9 ± 15.3 mmHg. There was no ventricular tachycardia, ventricular fibrillation, or second- or third-degree atrioventricular block. CONCLUSION: Regadenoson stress MPI appears to be well tolerated and safe in patients with PH.

Regadenoson use in chronic kidney disease and end-stage renal disease: A focused review.

Regadenoson is a selective A2A adenosine receptor agonist that has been approved as a vasodilator stress agent with single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI). Since its approval by the Food and Drug Administration (FDA) in 2008, it has become the most commonly used pharmacologic stress agent with SPECT-MPI. Given that it is predominantly renally excreted, its use in patients with chronic kidney disease has been the subject of active post-marketing clinical research. Until recently, prescribing information regarding the use of regadenoson in patients with end-stage renal disease (ESRD) was not defined in the package insert. Based on accumulating data since its initial approval, the FDA has recently outlined the use of regadenoson in patients with ESRD in a label update on January 17, 2017. In this review, we discuss the evidence leading to the recent label update, focusing on the pharmacokinetics of regadenoson in patients with impaired kidney function, the safety and tolerability of regadenoson in patients with chronic kidney disease and ESRD, and the prognostic value of regadenoson stress MPI in this patient population.

Influence of body mass index and type of low-level exercise on the side effect profile of regadenoson.

PURPOSE: Regadenoson, an A2A adenosine receptor pharmacologic stress agent for radionuclide myocardial perfusion imaging (MPI), is administered as a single, fixed dose. We studied the side effect profile of regadenoson combined with two types of low-level exercise, according to body mass index (BMI). METHODS: Three hundred and fifty-six patients (46.1% men, mean age 67.7±10.7 years, range 31-90 years) underwent regadenoson stress testing combined with low-level exercise. Subjects were classified according to BMI as normal, overweight, or obese, and the type of low-level exercise performed as walking on the treadmill (TE group, n=190) or forcefully swinging legs while sitting (SS group, n=166). Patients' demographics, medical history, clinical symptoms during stress, changes in ECG, oxygen saturation (SatO2), systolic blood pressure (SBP), and heart rate (HR) were evaluated. RESULTS: Groups were comparable (p=ns) with regard to cardiovascular risks factors. The incidence of side effects was similar across BMI (p=ns), although the TE patients showed improved profiles over those with SS exercise, with a significantly lower incidence of flushing, dizziness and nausea/gastrointestinal discomfort (12.9% vs. 28.4%; 19.9% vs. 33.4%; 11.4% vs. 19.2%, respectively; all p<0.05). Regarding the hemodynamic response, we did not observe significant changes in SBP and HR after regadenoson administration across BMI categories. Comparing the TE and SS groups, no significant changes were observed in SBP, but there was a higher increase in HR in the TE group (p<0.05). CONCLUSIONS: Regadenoson in combination with low-level exercise is safe and well tolerated over a wide range of BMI, with TE exercise showing a better side effect profile than SS.

Regadenoson versus Dipyridamole: A Comparison of the Frequency of Adverse Events in Patients Undergoing Myocardial Perfusion Imaging.

STUDY OBJECTIVE: To compare the frequency of adverse events in patients undergoing myocardial perfusion imaging (MPI) with either regadenoson or dipyridamole. DESIGN: Single-center, retrospective cohort study. SETTING: Large community teaching hospital. PATIENTS: A total of 568 adults who underwent single-photon emission tomography MPI with either regadenoson (284 patients) or dipyridamole (284 patients) as a vasodilator agent, following an institution conversion from regadenoson to dipyridamole in the MPI protocol on July 15, 2013, for cost-saving purposes. MEASUREMENTS AND MAIN RESULTS: Data were collected from the patients' electronic medical records. The primary endpoint was the composite occurrence of any documented adverse event in each group. Secondary endpoints were individual components of the primary endpoint, reason for termination of the MPI examination (protocol completion or premature end due to an adverse event), use of an interventional agent to an treat adverse event, and cost-related outcomes. A higher proportion of patients in the regadenoson group experienced an adverse event than those who received dipyridamole (84.9% vs 56.7%, p<0.0001). None of the patients in either group required early MPI study termination due to an adverse event. No significant differences were noted between groups regarding use of aminophylline or other interventions to treat adverse events. The overall drug cost savings in the postconversion dipyridamole group was $51,526. CONCLUSION: Dipyridamole was associated with fewer adverse events than regadenoson in patients undergoing MPI. Dipyridamole offers a safe and cost-effective alternative to regadenoson for cardiac imaging studies.

Safety of regadenoson in patients with severe chronic obstructive pulmonary disease.

OBJECTIVE: To assess the safety of regadenoson, a selective agonist of A2A adenosine receptors, combined with low-level exercise in subjects with severe chronic obstructive pulmonary disease (COPD), referred for myocardial perfusion imaging (MPI). METHODS: We studied prospectively 12 male patients with severe COPD. Stress was 4min of low-level exercise with bolus injection of regadenoson (0.4mg) at 1.5min, followed by (99m)Tc-MPI agent injection. Demographics, medical history, lung medications, adverse events, oxygen saturation (SatO2), MPI findings for coronary artery disease (CAD), and changes in systolic blood pressure (SBP), and heart rate (HR) were registered. RESULTS: The observed adverse event profile of regadenoson was similar to that of patients with mild-moderate COPD. There was no clinical exacerbation of COPD. Adverse events were self-limiting: dyspnea (33.3%), fatigue (25.0%), chest pain, headache (16.7%, respectively), and gastrointestinal discomfort, dry mouth, flushing, feeling hot and dizziness (8.3%, respectively). 25.0% of patients did not report any symptoms. We observed significant increases in SBP and HR from baseline (142.6mmHg±22.3 vs 152.5mmHg±18.5, and 80 b.p.m.±18 vs 105 b.p.m.±22, respectively; p<0.05). CONCLUSIONS: Regadenoson combined with low-level exercise is safe and well tolerated in stable patients with severe COPD undergoing MPI.

Safety and tolerability of regadenoson for myocardial perfusion imaging - first Danish experience.

OBJECTIVES: Evaluating safety and tolerability of the selective A2A receptor agonist, regadenoson, in patients referred for single photon emission computed tomography myocardial perfusion imaging (MPI). DESIGN: Observational study of patients referred for MPI stress testing using a 400 µg regadenoson (Rapiscan(®)) bolus. Hemodynamic variables and severity of adverse events (AE) were recorded before, during, and after administration. RESULTS: A total of 232 patients were included. One or more AE were reported in 90% of patients; the AEs were graded mostly mild to moderate in severity, resolved spontaneously, and were mainly dyspnea, headache, and chest pain. No advanced heart block or bronchospasm were seen. Transient ST-segment changes developed in 10 patients. The maximum increase in heart rate was 19 ± 11 beats/minute. The mean systolic blood pressure decreased from 144 to 139 mmHg (p < 0.0001). Medical intervention was required in three patients: one case with severe hypotension and two cases with chest pain that was relieved with sublingual nitroglycerin. One patient died the day after stress MPI for reasons considered unrelated to regadenoson. CONCLUSION: Regadenoson for MPI is easy to use with a high frequency of AEs, which are generally mild in severity, transient, and resolve spontaneously.

ST Segment Elevation ECG Changes During Pharmacologic Stress With Regadenoson.

Regadenoson is a pharmacologic stress agent that has been widely adopted as an alternative over other pharmacologic vasodilator agents due to its ease of use, patient tolerance, and safety profile. We report the case of dynamic ST-segment elevation electrocardiogram changes after regadenoson injection during an inpatient single-photon emission computed tomography myocardial perfusion stress test, with subsequent coronary angiography revealing the presence of hemodynamically significant coronary artery disease. Our findings confirm that transient regadenoson-induced ST-segment elevations are a marker for hemodynamically significant disease even in the setting of low-risk SPECT perfusion images.

Severe chronic kidney disease as a predictor of benefit from aminophylline administration in patients undergoing regadenoson stress myocardial perfusion imaging: A substudy of the ASSUAGE and ASSUAGE-CKD trials.

BACKGROUND: Regadenoson is predominantly renally metabolized. Patients with severe chronic kidney disease (CKD) experience more frequent gastrointestinal adverse effects (AE) from regadenoson. Aminophylline use following regadenoson reduces the incidence of regadenoson-related AE. We investigated whether patients with severe CKD receive incremental benefit from aminophylline administration in reducing regadenoson AE. METHODS: We performed post hoc analysis of the pooled database of the ASSUAGE and ASSUAGE-CKD trials. These were randomized placebo-controlled clinical trials which tested the benefit of intravenous aminophylline vs placebo after regadenoson injection in patients undergoing a clinically indicated stress MPI. Patients were categorized into two treatment arms: aminophylline vs placebo; and two groups: Severe CKD (GFR < 30 mL·min(-1)/1.73 m(2) or dialysis) and Control (GFR ≥ 30 mL·min(-1)/1.73 m(2)). The study endpoints were gastrointestinal AE, non-gastrointestinal AE and composite of any regadenoson AE. RESULT: The pooled database of the two trials yielded 548 patients, of whom 274 patients received aminophylline and 274 received placebo. Aminophylline was associated with greater absolute risk reduction (ARR) in gastrointestinal AE among patients with severe CKD vs controls (25% vs 4%, p < .001). A significant interaction was identified between severe CKD and aminophylline in reducing gastrointestinal AE (p = .007), indicating greater reduction in gastrointestinal AE with aminophylline use among patients with severe CKD. Aminophylline use was associated with a trend toward greater ARR in any regadenoson-related AE (32% vs 21%, p = .08). CONCLUSION: Aminophylline is associated with incremental benefit in reducing gastrointestinal AE in patients with severe CKD undergoing regadenoson stress MPI. Potentially, this population could be targeted for prophylactic administration of aminophylline in order to improve their overall experience with the test.