Blunted heart rate response to regadenoson predicts cardiovascular risk beyond quantitative positron emission tomography myocardial blood flow.

OBJECTIVE

To evaluate the incremental prognostic value of a blunted heart rate response (HRR) to regadenoson beyond PET-derived myocardial flow parameters.

BACKGROUND

A blunted HRR during pharmacologic stress with regadenoson, an adenosine A2A receptor agonist, may reflect autonomic dysfunction and heightened cardiovascular (CV) risk. Whether HRR provides prognostic information beyond stress myocardial blood flow (sMBF) and myocardial flow reserve (MFR) remains uncertain.

METHODS

We retrospectively analyzed consecutive rest-stress 82Rb PET/CT studies performed between 2016 and 2022. Abnormal sMBF and MFR were defined as less than 1.8 mL/min/g and <2.0, respectively. HRR was calculated as (peak HR - rest HR)/rest HR and considered blunted if less than 20%. We compared differences in major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or heart failure hospitalization) between patients with blunted and normal HRR using multivariable Cox regression, stratified by sMBF and MFR. Nonlinear associations between HRR and MACE were evaluated using restricted cubic splines. Incremental prognostic value was assessed by changes in the area under the receiver-operating characteristic curve (AUC) and net reclassification index (NRI).

RESULTS

Among 4611 patients (63 ± 11 years; 54% female), 1263 (27%) had blunted HRR. These patients had a higher prevalence of abnormal sMBF (49% vs 27%) and MFR (66% vs 30%). Over a median follow-up of 3.3 years (IQR 1.8-5.1), MACE rates were higher among patients with blunted HRR (16.2 vs 5.5 events/100 patient-years; adjusted HR 1.70 [95% CI: 1.50-1.94]; P < .001), irrespective of sMBF or MFR status. Risk increased progressively with lower HRR. Adding HRR to a model with key clinical characteristics and MBF improved prognostic discrimination and reclassification (ΔAUC +0.017; NRI 0.12; all P < .001).

CONCLUSIONS

Blunted HRR to regadenoson is independently associated with higher CV risk and provides incremental prognostic value beyond PET myocardial flow.