PurposeRegadenoson was approved for clinical use in Europe in 2011. Since then, it has become the default form of stress at our institution. We have assessed the side-effect profile and tolerability of regadenoson in patients undergoing clinically indicated myocardial perfusion scintigraphy between July 2011 and July 2012.MethodsClinical, stress and imaging data were recorded prospectively. Symptoms during stress were recorded and defined as mild, moderate or severe. An adverse event was defined as any symptom that persisted for more than 30 min or that required investigation or treatment.ResultsOf 1,764 consecutive patients, 1,581 (90 %) received regadenoson combined with submaximal exercise unless contraindicated. Symptoms were common (63 %) but transient and well-tolerated. The severity of symptoms was recorded in most patients as mild (84 %). Dyspnoea (36 %) and chest discomfort (12 %) were the commonest side effects. Adverse events were reported in eight patients (0.5 %), thought to be vasovagal in seven of these. All patients recovered fully without sequelae. There were no deaths, myocardial infarction or hospital admissions. Regadenoson stress was performed in 206 patients (12 %) with asthma or chronic obstructive pulmonary disease (COPD) without bronchospasm or any other major side effect.ConclusionWe studied the symptom profile of regadenoson in the largest European cohort to date. Regadenoson combined with submaximal exercise was well tolerated, notably also in patients with asthma or COPD. The majority of regadenoson-related adverse events were vasovagal episodes without sequelae.

Regadenoson was first approved by the US Food and Drug Administration in 2008 and the USA has the largest experience of its use. The European Medicines Agency gave approval in 2010 and we were the first site outside the Americas to use regadenoson in routine clinical practice. We were therefore surprised to encounter a number of adverse events consisting of bradycardia and hypotension occurring shortly after administration because such episodes had not previously been published. The recent report in this journal of two instances of asystole related to regadenoson indicates that the phenomenon is not unique to our practice. 1Following the report of our first year's experience, 2 occasional vaso-vagal reactions have continued, albeit at a very low frequency. Regadenoson remains our default form of pharmacological stress for myocardial perfusion scintigraphy, but we have become cautious in using it in patients who may not be able to tolerate prolonged hypotension, such as those with severe ischemic left ventricular dysfunction, severe left ventricular outflow obstruction, known cerebrovascular disease and the elderly.We have not been able to identify any predisposing features for bradycardia and hypotension but we have an unproven hypothesis that submaximal exercise and distraction with conversation reduces the risk. A few severe episodes have been preceded by nausea and retching and this may provide a pointer to the mechanism. Although speculative, the association with nausea points to vagal stimulation initiated by A2 receptors in the area postraema, a medullary structure in the floor of the fourth ventricle related to vomiting and autonomic control. Another observation that supports this hypothesis is that we have not been successful in reversing them with aminophylline. One patient with a prolonged sinus bradycardia of 20/minutes and unrecordable blood pressure did not respond to a total of 250 mg aminophylline IV over 2 minutes but did respond within 30 seconds to 0.6 mg atropine IV.Those who use regadenoson should therefore consider the risk of vagal stimulation in each patient and choose an appropriate form of stress. They might also consider atropine in patients with regadenoson-induced bradycardia and/or hypotension that does not respond to simple measures such as head-down posture and/or gentle leg exercise.

1. The changes in peak expiratory flow rate (PEF) and plasma cortisol were studied in relation to a 6 min period of treadmill running in six normal and eighteen asthmatic subjects. Of the asthmatics patients, five were not receiving treatment with steroids, six were receiving low doses of steroids (under 7.5 mg of prednisone daily) and seven were receiving high doses of steroids (over 7.5 mg of prednisone daily) at the time of study.2. All subjects were studied twice within 1 week at similar times of day, once after premedication with sodium cromoglycate (SCG) and once after a placebo.3. Resting PEF and plasma cortisol did not differ between placebo and SCG tests. 4. No change in PEF occurred as a result of exercise in the control subjects. The asthmatic patients developed post-exercise bronchoconstriction which was partly prevented by SCG but was not affected by steroids.5. Plasma cortisol rose after exercise in the asthmatic subjects but not in the control subjects. The rise may have been related to the stress of exercise-induced asthma. SCG had no significant effect on plasma cortisol after exercise.

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