Abstract
Background
Regadenoson is a novel selective A2A adenosine receptor agonist, which is administered as an intravenous bolus at a fixed dose. It is currently not clear if the absolute flow increase in response to this fixed dose is a function of distribution volume in individual patients or if it is generally comparable to the previous standard agents dipyridamole or adenosine, which are dosed based on weight. We used quantitative analysis of clinical 82Rb PET/CT studies to obtain further insights.
Methods
A total of 104 subjects with normal clinical rest/stress 82Rb perfusion PET/CT were included in a retrospective analysis. To rule out confounding factors, none had evidence of prior cardiac disease, ischaemia or infarction, cardiomyopathy, diabetes with insulin use, calcium score >400, renal disease or other significant systemic disease. A group of 52 patients stressed with regadenoson were compared with a group of 52 patients stressed with dipyridamole before regadenoson became available. The groups were matched for clinical characteristics, risk factors and baseline haemodynamics. Myocardial blood flow (MBF) and myocardial flow reserve (MFR) were quantified using a previously validated retention model, after resampling of dynamic studies from list-mode 82Rb datasets.
Results
At rest, heart rate, blood pressure and MBF were comparable between the groups. Regadenoson resulted in a significantly higher heart rate (34 ± 14 vs. 23 ± 10 beats per minute increase from baseline; p < 0.01) and rate–pressure product. Patients in the regadenoson group reported less severe symptoms and required less aminophylline. Stress MBF and MFR were not different between the groups (2.2 ± 0.6 vs. 2.1 ± 0.6 ml/min/g, p = 0.39, and 2.9 ± 0.8 vs. 2.8 ± 0.7, p = 0.31, respectively). In the regadenoson group, there was no correlation between stress flow or MFR and body weight or BMI.
Conclusion
Despite its administration at a fixed dose, regadenoson results in an absolute increase in MBF which is comparable to that following dipyridamole administration and is independent of patient distribution volume. This further supports its usefulness as a clinical stress agent.
Similar content being viewed by others
References
Bengel FM, Higuchi T, Javadi MS, Lautamaki R. Cardiac positron emission tomography. J Am Coll Cardiol. 2009;54(1):1–15.
Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary artery disease. Circulation. 2007;115(11):1464–80.
Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99 m sestamibi SPECT. J Nucl Cardiol. 2006;13(1):24–33.
Gould KL, Ornish D, Scherwitz L, Brown S, Edens RP, Hess MJ, et al. Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification. JAMA. 1995;274(11):894–901.
Lertsburapa K, Ahlberg AW, Bateman TM, Katten D, Volker L, Cullom SJ, et al. Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol. 2008;15(6):745–53.
Yoshinaga K, Chow BJ, Williams K, Chen L, de Kemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol. 2006;48(5):1029–39.
Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol. 1994;23(2):384–9.
Al Jaroudi W, Iskandrian AE. Regadenoson: a new myocardial stress agent. J Am Coll Cardiol. 2009;54(13):1123–30.
Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results. JACC Cardiovasc Imaging. 2008;1(3):307–16.
Hendel RC, Bateman TM, Cerqueira MD, Iskandrian AE, Leppo JA, Blackburn B, et al. Initial clinical experience with regadenoson, a novel selective A2A agonist for pharmacologic stress single-photon emission computed tomography myocardial perfusion imaging. J Am Coll Cardiol. 2005;46(11):2069–75.
Iskandrian AE, Bateman TM, Belardinelli L, Blackburn B, Cerqueira MD, Hendel RC, et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007;14(5):645–58.
Mahmarian JJ, Cerqueira MD, Iskandrian AE, Bateman TM, Thomas GS, Hendel RC, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: a quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging. 2009;2(8):959–68.
Lautamaki R, Brown TL, Merrill J, Bengel FM. CT-based attenuation correction in (82)Rb-myocardial perfusion PET-CT: incidence of misalignment and effect on regional tracer distribution. Eur J Nucl Med Mol Imaging. 2008;35(2):305–10.
Bravo PE, Chien D, Javadi M, Merrill J, Bengel FM. Reference ranges for LVEF and LV volumes from electrocardiographically gated 82Rb cardiac PET/CT using commercially available software. J Nucl Med. 2010;51(6):898–905.
Chander A, Brenner M, Lautamaki R, Voicu C, Merrill J, Bengel FM. Comparison of measures of left ventricular function from electrocardiographically gated 82Rb PET with contrast-enhanced CT ventriculography: a hybrid PET/CT analysis. J Nucl Med. 2008;49(10):1643–50.
Nekolla SG, Miethaner C, Nguyen N, Ziegler SI, Schwaiger M. Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography. Eur J Nucl Med. 1998;25(9):1313–21.
Yoshida K, Mullani N, Gould KL. Coronary flow and flow reserve by PET simplified for clinical applications using rubidium-82 or nitrogen-13-ammonia. J Nucl Med. 1996;37(10):1701–12.
Lautamaki R, George RT, Kitagawa K, Higuchi T, Merrill J, Voicu C, et al. Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis. Eur J Nucl Med Mol Imaging. 2009;36(4):576–86.
Czernin J, Muller P, Chan S, Brunken RC, Porenta G, Krivokapich J, et al. Influence of age and hemodynamics on myocardial blood flow and flow reserve. Circulation. 1993;88:62–9.
Leaker BR, O'Connor B, Hansel TT, Barnes PJ, Meng L, Mathur VS, et al. Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: a randomized, double-blind, placebo-controlled trial. J Nucl Cardiol. 2008;15(3):329–36.
Thomas GS, Tammelin BR, Schiffman GL, Marquez R, Rice DL, Milikien D, et al. Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial). J Nucl Cardiol. 2008;15(3):319–28.
Lieu HD, Shryock JC, von Mering GO, Gordi T, Blackburn B, Olmsted AW, et al. Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol. 2007;14(4):514–20.
Gaemperli O, Schepis T, Koepfli P, Siegrist PT, Fleischman S, Nguyen P, et al. Interaction of caffeine with regadenoson-induced hyperemic myocardial blood flow as measured by positron emission tomography: a randomized, double-blind, placebo-controlled crossover trial. J Am Coll Cardiol. 2008;51(3):328–9.
Dhalla AK, Wong MY, Wang WQ, Biaggioni I, Belardinelli L. Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther. 2006;316(2):695–702.
Disclosures
This study was not supported by a sponsored research grant. Dr. Bengel has been a consultant to Lantheus Medical Imaging, Astellas Pharma and GE Healthcare, received research funding from Lantheus Medical Imaging and GE Healthcare, and received speaker honoraria from GE Healthcare, Siemens Medical Solutions and BayerSchering Pharma. Mrs. Merrill received speaker honoraria from Astellas Pharma. The other authors report no conflicts.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Goudarzi, B., Fukushima, K., Bravo, P. et al. Comparison of the myocardial blood flow response to regadenoson and dipyridamole: a quantitative analysis in patients referred for clinical 82Rb myocardial perfusion PET. Eur J Nucl Med Mol Imaging 38, 1908–1916 (2011). https://doi.org/10.1007/s00259-011-1853-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-011-1853-6