Optimising quantitative myocardial perfusion CMR with regadenoson: effects of post-stress timing and protocol design

Aims Fully automated quantitative perfusion cardiovascular magnetic resonance (CMR) enables absolute myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) mapping. However, current clinical protocols are largely extrapolated from adenosine, despite the increasing use of regadenoson, which exhibits distinct pharmacokinetics. This study aimed to (i) compare quantitative MBF and MPR obtained with regadenoson and adenosine using standard stress-first protocols, (ii) determine the impact of the post-stress pause duration on resting MBF and MPR after regadenoson, and (iii) evaluate a regadenoson rest–stress–rest (RSR) protocol as an alternative strategy for accurate quantitative perfusion assessment. Methods In this prospective single-centre study, 120 consecutive patients referred for clinically indicated stress CMR were enrolled; 116 met all quality criteria and were included in the final analysis. All examinations were performed at 1.5 T using dual-sequence first-pass perfusion imaging with fully automated pixel-wise MBF and MPR mapping. Four regadenoson stress-first groups were studied with nominal pause intervals of 10, 12, 15, and 18 minutes between stress and first rest perfusion. All regadenoson patients underwent an additional late rest acquisition. A standard adenosine stress-first group and a regadenoson RSR group served as comparators. Results Stress MBF did not differ between adenosine and regadenoson (median ~2.3–2.5 ml/min/g; p > 0.05), indicating comparable peak hyperaemia. In contrast, early post-stress resting MBF was significantly higher after regadenoson than after adenosine, particularly at 10–15 minutes, resulting in markedly reduced MPR (median ~1.6–1.9 vs. ~3.1; p < 0.001). With increasing pause duration, resting MBF progressively declined and MPR increased, approaching physiological reference ranges only beyond approximately 25–30 minutes after stress. The regadenoson RSR protocol yielded resting MBF and MPR values comparable to adenosine and to established normal ranges. Conclusions Although regadenoson provides stress MBF comparable to adenosine, standard stress-first protocols with short post-stress pauses substantially overestimate resting MBF and underestimate MPR due to persistent residual hyperaemia. For accurate quantitative perfusion CMR, regadenoson protocols should incorporate either a substantially prolonged post-stress pause or a rest–stress–rest acquisition strategy.