EditorialAdverse effects associated with regadenoson myocardial perfusion imaging
Introduction
Single-photon emission computed tomography myocardial perfusion imaging (MPI) is one of the most widely used non-invasive methods for assessing patients with known or suspected coronary artery disease (CAD).1 Exercise is the preferred stressor, however, in cases of patients who either cannot exercise adequately or there are contraindications to exercise, vasodilating agents can be used instead. Of these, regadenoson is the only FDA-approved A2A adenosine receptors selective agonist; due to its selectivity and ease of use, it is the stressing agent of choice in the United States and its use is increasing in other countries. After binding to A2A receptors on smooth muscle cells, regadenoson leads to vasodilatation, predominantly of the coronary bed and secondarily of the periphery. The majority of the administered dose is renally excreted (58% of the administered dose)2 and its clearance is prolonged in individuals with impaired renal function.3
In addition to its ease of administration (single bolus of 200 mcg given intravenously, IV), when compared to adenosine, regadenoson has been shown to be non-inferior for identifying perfusion defects4 and providing prognostic data.5, 6, 7, 8, 9, 10 Furthermore, it is better tolerated as evidenced by a lower summed score of chest pain, dyspnea, and flushing reported by the patients4 and has a comparable safety profile.4 Despite its advantages, there still are certain undesirable effects associated with the use of regadenoson, the incidence of which is overall low. Nevertheless, it is clinically important to not only recognize these undesirable effects, but also to manage them appropriately.
In this issue of the Journal, Agrawal et al. describe two patients who underwent regadenoson MPI and experienced chest pain during the test.11 In the first patient, treatment with oral nitroglycerin worsened symptoms, led to the development of hypotension and evolution of electrocardiographic (ECG) changes with initially persistent ST-segment depression followed by ST elevation. Resting MPI and coronary angiography revealed severe multi-vessel CAD. The second patient complained of chest pain after receiving regadenoson along with evidence of ST-segment depression. Both the symptoms, as well as the ECG changes resolved following administration of IV aminophylline and the patient was able to complete his stress test. Similarly to the first case, severe multi-vessel CAD was evident on MPI and coronary angiography. The two case examples of differential response to nitroglycerin vs aminophylline serve to stress the importance of recognizing adverse effects seen with regadenoson MPI and the proper management strategies that should be used. The authors conclude that in patients with severe underlying CAD, development of chest pain and ECG changes after regadenoson most likely represents coronary steal. In such cases, nitroglycerin has the risk of causing further steal and clinical deterioration, as opposed to aminophylline which may offer benefit by ameliorating the extent of steal and resolving patient symptoms.11
Section snippets
Cardiovascular Adverse Effects
The differential management and immediate clinical response of these two cases exemplify the importance of knowledge of the potential side effects associated with use of regadenoson and what the optimal antidote is. In the landmark ADVANCE-MPI trial, chest pain and shortness of breath were among the most frequently reported side effects of regadenoson (29% and 28%, respectively).4 Episodes of fatal and non-fatal myocardial ischemia and infarction have also been reported in association with
Non-cardiovascular Adverse Effects
Given its high selectivity for the A2A receptors, regadenoson was initially anticipated to have been free of pulmonary-related side effects due to A2B and A3 receptor activation. Initial large-scale trials using regadenoson either excluded patients with known bronchospastic/bronchorestrictive lung disease or only allowed for inclusion of a small fraction of patients with known COPD or asthma (range 6%-16%).4,35,39,40 Following initial post-marketing reports of wheezing, dyspnea, and respiratory
Conclusion
As the population ages, use of vasodilators with MPI instead of exercise will continue to rise. A2A selective agonists, such as regadenoson, are easier to use and associated with better safety and tolerability profiles than non-selective agents such as adenosine and dipyridamole. Despite its advantage and its diagnostic and prognostic value, clinicians should be aware of the side effects associated with regadenoson. The vast majority of these side effects are short-lived, benign, and
Disclosure
Dr. Hage reports investigator-initiated grant support from Astellas Pharma. Efstathia Andrikopoulou has no disclosure.
Funding
Dr. Hage has received research grants from Astellas Pharma USA.
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See related article, https://doi.org/10.1007/s12350-017-1174-7.
A correction to this article is available online at https://doi.org/10.1007/s12350-018-1281-0.