Safety and feasibility of regadenoson use for suboptimal heart rate response during symptom-limited standard Bruce exercise stress test

Abstract

Background: Regadenoson during exercise stress test (ETT) can provide maximal hyperemia for myocardial perfusion imaging (MPI), along with exercise information. Our aim was to study the feasibility and safety of regadenoson injection at peak ETT for submaximal heart rate (HR) response.

Methods: Consecutive patients who underwent SPECT MPI with standard Bruce ETT or supine-regadenoson (Supine-Reg) were analyzed. ETT patients were grouped as ETT-Max [maximal HR > 0.85 * (220 - age), N = 1,522], ETT-Submax (submaximal HR no regadenoson, N = 504), ETT-Reg (submaximal HR and regadenoson, N = 211).

Results: The HR during ETT was submaximal in 715 (32%) patients. Of these, 211 patients (30%) underwent ETT-Reg (mean exercise duration: 5.5 ± 2.5 minutes). ETT-Reg patients had a higher frequency of hypertension, diabetes, smoking and beta-blocker use, similar rest systolic blood pressure (SBP), but lower rest and peak HR and peak SBP compared to ETT-Max patients. There were no serious complications with regadenoson. Side effects (49% vs 6%, P < .0001) were fewer and aminophylline use was lower with ETT-Reg compared to Supine-Reg (0.5% vs 8.1%, P = .001).

Conclusions: Submaximal HR response to ETT is common. ETT-Reg is safe, feasible, and well-tolerated. ETT-Reg facilitates a diagnostic MPI with reporting of functional capacity, exercise ECG/hemodynamic changes and MPI at maximal hyperemia.

Figure 1. ETT-Reg Protocol

This figure shows the steps of regadenoson injection during maximal symptom-limited standard Bruce treadmill test (ETT-Reg). MPI = myocardial perfusion imaging. HR = heart rate; BP = blood pressure; IV = intravenous, Tc=^99mTechnetium sestamibi.

Figure 2. Patient Selection

This figure shows the selection of patients for the ETT-Reg protocol. All patients were selected as a Supine-regadenoson (unable to exercise) or as an ETT (able to exercise on a standard Bruce protocol). In patients who underwent an ETT, those who attained >85% of the age predicted maximal heart rate (220-age) received radiotracer injection and the test was completed. Among the patients who did not attain maximal heart rate, and did not have known coronary artery disease or definite ischemic signs or symptoms, regadenoson was injected while the patient was still exercising on the treadmill. The rest of the patients received radiotracer injection irrespective of the heart rate.

Figure 3. Heart Rate and Blood Pressure Response to Stress

This figure demonstrates the rest and peak stress heart rate and blood pressure in patients undergoing an ETT-Max, ETT-Submax or ETT-Reg protocols. The peak stress heart rate and blood pressure were significantly different between each of the groups (ANOVA with post hoc tests P <0.0001 for each comparison vs. ETT-Max).

Figure 4. Tolerability and ST-Segment Changes With Regadenoson

This figure demonstrates the frequency of chest pain, dyspnea, ST segment depression and symptoms consistent with regadenoson (flushing, dizziness, gastrointestinal symptoms or headache), in the ETT-Max, ETT-Submax, ETT-Reg and Supine-Reg groups. Chest pain was most frequent in the ETT-Submax group, dyspnea was most frequent in the ETT-Reg group, and ST segment depression was most frequent in the ETT-Max group. Symptoms consistent with regadenoson use (Reg) were most frequent in the Supine-Reg group.