Effect of aminophylline administration on the diagnostic yield of vasodilator myocardial perfusion imaging

Abstract

The last few decades have witnessed a steady increase in the proportion of myocardial perfusion imaging (MPI) tests that utilize pharmacologic stress instead of exercise. 1 Currently regadenoson, a pyrazole derivative of adenosine selective for the A 2A receptor, is the most commonly used vasodilator agent accounting for more than 80% of all pharmacological stress tests performed in the USA. 2 The widespread utilization of regadenoson is supported by multiple factors including its similar diagnostic and prognostic performance to adenosine when used for MPI, the simpler and more rapid infusion protocol, and the better safety profile in specific patient groups. 3-6 Although better tolerated by patients, regadenoson shares with adenosine similar adverse effects such as flushing, headaches, and gastrointestinal symptoms. 3,7 Aminophylline, a nonselective adenosine receptor antagonist, has been available on the market for decades and used to reverse the adverse effects of dipyridamole and adenosine and more recently been shown to be safe and effective for use with regadenoson. 8,9 In this issue of the Journal, Fughhi et al. 10 address the concern that use of aminophylline to ameliorate the adverse effects of regadenoson may reverse its effects on coronary vasodilation and subsequent myocardial hyperemia reducing the sensitivity of MPI for detecting perfusion abnormalities. The data for the current study were pooled from two double-blinded, placebo-controlled randomized clinical trials, the ASSUAGE and ASSUAGE-CKD trials, 9,11 which demonstrated the effectiveness of aminophylline in attenuating the adverse effects associated with regadenoson in patients undergoing MPI. In both trials, patients were randomized to receive 75 mg of intravenous aminophylline or placebo administered at 90 seconds after radioisotope injection (*2 minutes following regadenoson). The primary end point of the current report was the degree of reversibility of the perfusion defect on imaging as measured by the semi-quantitative summed difference score (SDS). The secondary end point was the presence of myocardial ischemia as defined by SDS C2. The authors also examined the effect of aminophylline use on the prognostic value of myocardial ischemia detection by MPI for cardiac events including cardiac death, myocardial infarction (MI), and coronary revascularization over a follow-up period of 29 ± 14 months.The myocardial ischemic burden (primary outcome) and the presence of myocardial ischemia (secondary outcome) on MPI were similar between the two groups. However, there was a trend towards a higher proportion of abnormal perfusion (summed stress score, SSS C4, 34% vs 27%, P = .08) in the placebo group that the authors attributed to the significantly higher rate of prior MI (20% vs 13%, P = .03) in this group. To account for this imbalance, the authors performed a sensitivity analysis in patients without clinical or MPI evidence (summed rest score, SRS C4) of prior MI, and demonstrated similar prevalence of myocardial ischemia and abnormal perfusio...

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR

“…The guidelines reflect evidence that most vasodilator stress-related adverse effects are self-limiting and do not require reversal. Serious adverse effects can be effectively aborted with IV administration of aminophylline, a xanthine derivative and a nonselective adenosine receptor antagonist,2 with the exception of seizures. IV lorazepam should be the first-line intervention for seizures and methylxanthine use is not recommended for reversal of adenosine or regadenoson effects under these circumstances because of the concern for possible lowering of the seizure threshold and potential risk of exacerbating seizures,3 based on limited evidence and the preponderance of expert opinion.…”

Clinical and economic outcomes of pharmacological stress tests in patients with a history of COVID‐19

“…Reversal agent use was defined by procedure codes or National Drug Code on the index date. Among those requiring reversal agent use, a prespecified diagnosis was sought as a potential indication of reversal agent use 14–17 . Thirty‐day all‐cause costs after pharmacologic MPI (in US dollars [USD]) were assessed among patients excluding the Medicare Supplemental population because this database does not capture the Medicare part of the payment.…”

“…Guidelines recommend regadenoson as the preferred coronary vasodilator agent for pharmacologic MPI during the pandemic 9 due to its shorter infusion time (10 seconds) compared with several minutes for adenosine and dipyridamole, which helps to minimize contact time between health professionals and patients 11–13 . In the event of serious or intolerable adverse effects during pharmacologic MPI, reversal agents such as caffeine and the adenosine receptor antagonist (aminophylline) can be administered to reverse the effects of the vasodilator agent 14–17 . In the regadenoson phase 3 trials of 2015 patients undergoing pharmacologic MPI (median [range] age: 66 [26–93] years; primarily White males), 3% of patients receiving regadenoson ( n = 46/1337) and 2% of those receiving adenosine ( n = 12/678) received reversal agents 11,18 .…”

Aminophylline shortage and current recommendations for reversal of vasodilator stress: an ASNC information statement endorsed by SCMR

“…The guidelines reflect evidence that most vasodilator stress-related adverse effects are self-limiting and do not require reversal. Serious adverse effects can be effectively aborted with IV administration of aminophylline, a xanthine derivative and a nonselective adenosine receptor antagonist [2], with the exception of seizures. Intravenous lorazepam should be the first-line intervention for seizures and methylxanthine use is not recommended for reversal of adenosine or regadenoson effects under these circumstances because of the concern for possible lowering of the seizure threshold and potential risk of exacerbating seizures [3], based on limited evidence and the preponderance of expert opinion.…”