Heart rate response during vasodilator stress myocardial perfusion imaging: Mechanisms and implications

Abstract

See related article, pp. 617-624Myocardial perfusion imaging (MPI) using adenosine, dipyridamole, or regadenoson (a selective A 2A receptor agonist) is an established method for detecting coronary artery disease (CAD) and risk stratification. 1 In high-risk populations, as in those with diabetes mellitus (DM) or chronic kidney disease, MPI has been shown to be a powerful predictor of risk, but nevertheless, patients with normal myocardial perfusion are at higher risk than those without DM or chronic kidney disease. 2,3 Thus, there continues to be a need to extract more useful prognostic data from stress MPI especially in high-risk populations.A blunted heart rate (HR) response to exercise stress has been known to be an independent predictor of poor outcome and is used clinically in conjunction with other prognostic variables such as perfusion defects, left ventricular (LV) ejection fraction (EF) and volumes, exercise time, and symptoms during exercise to derive an overall assessment of risk in a particular patient. 4 In patients undergoing stress testing, for one reason or another, with adenosine or regadenoson (and dipyridamole, which acts indirectly by increasing interstitial levels of endogenous adenosine), there is a modest increase in HR and a modest decrease in blood pressure (BP). The increase in HR has been traditionally attributed to a reflex response to the vasodilatory effect on the systemic circulation and the resultant increase in sympathetic discharge. 5,6 The true mechanism of HR increase, however, is more complicated and involves direct stimulation of the sympathetic nervous system. 7 The administration of adenosine as a bolus, as done for the interruption of supra-ventricular tachycardias, has a negative chronotropic effect on the atrio-ventricular node via stimulation of the A1 receptor. This is in contradistinction to its effect on the A 2A receptor when given as an infusion in stress MPI studies where it induces an increase in HR. 5,8 The development of selective A 2A receptor agonists (such as regadenoson) has allowed for the dissection of the effects of adenosine on the multiple receptors. A well-done pivotal study in rats by Dhalla et al 7 that used regadenoson in combination with a selective A 2A receptor antagonist, B-blocker, a ganglionic blocker (to block the sympathetic nervous system), and a direct vasodilator (nitroprusside) demonstrated the dissociation of tachycardia and hypotension (secondary to peripheral vasodilation) responses to regadenoson. This and other data (reviewed in Ref. 9 ) confirm that A 2A receptor agonists cause a direct stimulation of the autonomic nervous system, which results in sinus tachycardia independent of the baroreflex mechanism. Thus, the change in HR in response to A 2A receptor agonists can be used to evaluate autonomic function.In order to evaluate the HR response to adenosine and regadenoson in relation to DM (since there is a high prevalence of autonomic dysfunction in patients with DM), we used data from the ADenoscan Versus RegAdenosoN Comparativ...

Heart rate response to regadenoson: Making the case for its value in clinical practice

“…25 Another interesting distinction is revealed by the study of Aljaroudi et al 8 In this study population that consisted exclusively of ESRD patients, the median and the quartiles of HRR were identical to the previously published distribution of HRR in 1156 consecutive …”

A blunted heart rate response to regadenoson is an independent prognostic indicator in patients undergoing myocardial perfusion imaging

“…23 We have previously noted that the HRR response to the clinically available agonists of the various A 2A receptor agonists is variable. 13 For example, regadenoson induces a higher HRR response than adenosine. 5,6 In a recent study, we defined a blunted HRR to adenosine as \10% (20% of the population) while in this study the lowest quartile had a HRR \17%.…”

“…[7][8][9][10][11][12] Since regadenoson induces a more intense increase in heart rate than adenosine, the prognostic information derived from adenosine studies can not be automatically applied to regadenoson. 5,6,13 This is the first study that examines the predictors and the prognostic value of the HRR to regadenoson with the hypothesis that the HRR carries incremental prognostic information to that derived from the perfusion pattern and the left ventricular (LV) ejection fraction (EF).…”

Safety of regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic kidney disease patients not on hemodialysis

“…Studies have shown that diabetes, metabolic syndrome, and renal dysfunction were independent predictors of blunted heart rate response to adenosine or regadenoson with the HR response being dissociated from BP response. 14 More specifically, in the study by Hage et al, 15 the HR response decreased by 0.7%/10 mL/min/1.73 m 2 decline in eGFR. This blunted heart rate response to pharmacologic vasodilators seems to carry adverse prognostic value and needs further evaluation with autonomic function studies.…”