Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus

doi:10.1016/j.ahj.2009.01.011

American Heart Journal

Volume 157, Issue 4, April 2009, Pages 771-776

https://doi.org/10.1016/j.ahj.2009.01.011 Get rights and content

Background

Adenosine and regadenoson increase heart rate (HR) when used as stress agents to produce coronary hyperemia due to direct sympathetic stimulation. We hypothesized that the HR response will be lower in patients with than in those without diabetes mellitus (DM).

Methods

We studied the HR response (percentage maximal increase) in 2,000 patients in The ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and 2) Trials with known DM status.

Results

There were 643 patients with a history of DM (65.4 ± 0.4 years, 32% women) and 1,357 patients with no DM (65.5 ± 0.3 years, 29% women). Compared with non-DM, the DM group had higher HR at baseline (68.4 ± 0.48 vs 65.2 ± 0.31 beat/min, P < .001) and smaller HR response after adenosine or regadenoson administration (29.4% ± 0.64% vs 36.1% ± 0.54%, P < .001). Insulin therapy was associated with further blunting in the HR response (25.9% ± 1.0% vs 31.2% ± 0.8%, P < .001). After adjusting for β-blocker intake, baseline HR, age, gender, renal function, systolic blood pressure, and left ventricular systolic function, DM independently accounted for a decrease in the HR response.

Conclusions

The HR response to adenosine and regadenoson in patients with DM is blunted. If additional studies confer an agreement between traditional tests for determination of autonomic neuropathy and this measure, then examination of HR response to these agents during myocardial perfusion imaging might add prognostic power.

Section snippets

Methods

The ADVANCE MPI Trials (registrations numbers at www.clinicltrials.gov are NCT00208299 and NCT00208312) are randomized multicenter phase 3 trials identically designed to demonstrate noninferiority by comparing the strength of agreement between sequential adenosine-regadenoson and adenosine-adenosine images for the detection of reversible perfusion defects. Both phase 3 trials independently showed that regadenoson is noninferior to adenosine for the detection of reversible defects and is safe

Results

The ADVANCE MPI Trials included 2,015 patients; of these, only 15 had uncertain DM status. The remaining 2,000 patients constituted the analysis set. Baseline characteristics of the patients according to their DM status are shown in Table I. In general, patients had similar age and gender distribution regardless of their DM status. The DM group was more obese and had a higher proportion of minorities, and its members were more likely to be hypertensive and have a diagnosis of CAD at entry.

Discussion

The aim of this study was to assess the HR response to selective (regadenoson) and nonselective (adenosine) A_2A agonists in patients with and without DM in the ADVANCE MPI Trials. We report that patients with DM had a lower (blunted) HR response to these agents and that this effect occurred independent of all other variables examined.

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Clinical InvestigationDiabetes and MetabolismDifferences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Cardiol

J Nucl Cardiol

J Am Coll Cardiol Img

J Nucl Cardiol

Pharmacol Ther

J Nucl Cardiol

Am J Cardiol

J Am Coll Cardiol

Circulation

Reproducibility of heart rate changes following adenosine infusion in man

Eur J Clin Pharmacol

Mechanism and pressor relevance of the short-term cardiovascular and renin excitatory actions of the selective A2A-adenosine receptor agonists

J Cardiovasc Pharmacol

Adenosine increases sympathetic nerve traffic in humans

Circulation

Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats

J Pharmacol Exp Ther

Clinical Investigation
Diabetes and Metabolism
Differences in heart rate response to adenosine and regadenoson in patients with and without diabetes mellitus