Regadenoson and exercise myocardial perfusion imaging: The courtship continues

American Society of Nuclear Cardiology (ASNC) guidelines support the use of low-level exercise testing for adenosine and dipyridamole in select patients to improve diagnostic accuracy and to decrease adverse side effects. Regadenoson does not have the same support in the current guidelines and, as with the adenosine and diypridamole, its use with exercise remains ‘‘off-label’’. Since approval in 2008, regadenoson has become the most common vasodilator stress test agent in the United States. Its ease of use as a single bolus injection makes it versatile and straightforward to use. Although approved for supine testing, it has been evaluated for low-level exercise (a protocol we characterize as RegLowEx) in one randomized trial and a large observational study. Similar to adenosine and dipyridamole, the goals of RegLowEx are improved image quality and decreased vasodilator associated symptoms. Newer studies have evaluated regadenoson given just before peak exercise (which we term RegNearPeakEx), at peak (termed RegPeakEx), and just after peak exercise (termed RegPostPeakEx) for those unable to achieve 85% of maximum predicted heart rate or meet an ischemic endpoint. The primary goal of protocols that allow patients to exercise to peak is to obtain prognostic information from the exercise stress aspect of the test and use regadenoson on an provisional basis such that perfusion imaging sensitivity is not compromised due to lack of an appropriate heart rate being achieved. A proposed algorithm was described in our previous editorial on this topic. A randomized clinical trial of a novel protocol in which symptom limited exercise is performed and if an adequate heart rate or an ischemic endpoint is not achieved, the administration of regadenoson is delayed until three minutes post exercise during a five minute recovery period of slow walking (termed RegRecovery) is now underway. In the current issue of the Journal, Cabrera and colleagues present an excellent contribution to the literature with the third study evaluating hemodynamic and stress testing variables in patients undergoing RegLowEx myocardial perfusion imaging (MPI). In this retrospective analysis of 485 patients who underwent RegLowEx protocol for MPI compared with 887 patients who underwent supine regadenoson imaging, the authors found the RegLowEx protocol to be safe. The use of aminophylline to reverse adverse effects was significantly lower in the RegLowEx group than the regadenoson supine group, 5.6% vs 11.4%, respectively. Understandably, in a retrospective analysis, the two study populations had different baseline characteristics. In their sample, subjects undergoing low-level exercise were significantly younger and had fewer comorbidities. Although resting heart rates were similar in the two groups (69 bpm in regadenoson group, 67 bpm in RegLowEx), as would be expected there was a more prominent increase in the RegLowEx group, 103 vs 83 bpm, respectively. On average, systolic blood pressure decreased by 9 mm Hg in the regadenoson only group but increased by 5 mm Hg in the low-level exercise group. Summed difference score on MPI was not significantly different although this comparison must be viewed with caution given the baseline differences between the study groups. The rate of common symptoms including headache, chest pain, and dyspnea was similar in both groups. Flushing and abdominal discomfort were more common in the regadenoson only group whereas dizziness and fatigue were more common in the RegLowEx group. The RegLowEx group included patients with left bundle branch block (LBBB). Similar to previous two studies, From the MemorialCare Heart & Vascular Center, Long Beach Memorial Medical Center and Miller Childrenos Hospital of Long Beach, Long Beach, CA; and Division of Cardiology, University of California, Irvine, CA. Reprint requests: Gregory S. Thomas, MD, MPH, FACC, FASNC, MemorialCare Heart & Vascular Center, Long Beach Memorial Medical Center and Miller Children’s Hospital of Long Beach, 2801 Atlantic Ave, Long Beach, CA 90806; gthomas1@memorialcare. org. J Nucl Cardiol 2013;20:324–8. 1071-3581/$34.00 Copyright 2013 American Society of Nuclear Cardiology. doi:10.1007/s12350-013-9695-1