Optimizing Protocols for Regadenoson Stress CMR: Impact of Pause Duration Between Stress and Rest Perfusion on Rest Myocardial Blood Flow and Myocardial Perfusion Reserve

Background: Regadenoson is increasingly used for pharmacological stress perfusion cardiac magnetic resonance imaging (S-CMR). Additionally, artificial intelligence based quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) has recently become clinically available. However, due to different pharmacodynamics compared to adenosine, the optimal protocol for CMR-derived MBF quantification using regadenoson remains unknown and was the objective of this prospective study.

Methods: A total of 144 participants, who underwent clinically indicated S-CMR at our institution in 2024 and gave informed consent were included. Patients with evidence of insufficient vasodilator stress (defined as: stress MBF (SMBF) <1.43 ml/g/min in all AHA segments, heart rate increase <10 bpm or blood pressure drop <10 mmHg) were excluded leaving n=136 for the final analysis. Out of 136 patients, 117 were assigned to groups with different pause intervals (10, 12, 15, and 18 minutes) between regadenoson stress and rest perfusion in an unblinded manner. The remaining 19 patients underwent a reversed stress-/rest-sequence, starting with rest perfusion subsequently followed by stress perfusion after 10 minutes. Another group of n=18 patients underwent the conventional adenosine S-CMR protocol and thus served as control group. All patients underwent an additional extra late rest perfusion scan at the end of the CMR exam to determine true rest perfusion.

Results: Study participants were on average 62 ± 11 years old and 52.9% were male. Analysis of MBF and MPR in patients with regadenoson stress applying the routine pause interval between rest and stress established for the use with an adenosin protocol (i.e. 10-minutes) led to overestimation of rest MBF (RMBF) by 59% (1.56±0.73 vs. 1.10±0.73, p<0.001) and consecutive underestimation of MPR (1.66±0.54 vs. 2.29±63, p<0.001) compared to true rest perfusion.

With increasing pause intervals (12min, 15min, and 18min), RMBF decreased and MPR increased, however, compared to true rest perfusion the RBMF was still overestimated even using an 18 min pause interval (RMBF 1.16±0.45 vs. 0.90±0.22, p=0.001; MPR 2.04±0.69 vs. 2.55±0.88, p<0.001). Interestingly, in patients with reversed sequence (rest perfusion followed by stress perfusion imaging), quantitative perfusion data were comparable to the adenosine control group (RMBF 0.85±0.23 vs. 0.86±0.25, p=0.86), SMBF (2.32±0.60 vs. 2.44±0.66, p=0.55) and MPR (2.78 ±0.67 vs. 2.96±0.93, p=0.51).

Conclusion: Our data demonstrate that residual hyperemia during rest perfusion results in a potentially clinically relevant overestimation of RMBF and thus an underestimation of MPR when routine adenosine S-CMR protocols are not adapted to the different pharmacodynamics of regadenoson. This may result in a substantial number of false-positive results of quantitative regadenoson S-CMR procedures regarding epicardial and/or microvascular coronary disease, with potential clinical implications on further patient care. Since prolongation of the pause interval after regadenoson stress up to 18 minutes does not allow for normalization of RBMF, a reversed protocol (rest perfusion first followed by stress perfusion) may be considered as a possible solution.