Potential advantage of a moderate increase in coronary blood flow (CBF) using vasodilators: Implications for an optimal dose of regadenoson

Objectives Regadenoson administered as i.v. bolus of 0.4 mg typically results in ~ 3.0-fold increase in CBF in non-ischemic territories (NIT). We hypothesized that such an increase may jeopardize detection of mild/moderate ischemia considering the low extraction fraction (EF) of current myocardial perfusion tracers at higher flow rates. We determined whether more moderate CBF increases lead to greater uptake deficits in ischemic territories (IT) caused by mild/moderate coronary artery stenosis (CAS).

Methods We used published data relating CBF to EF of 201Tl and 99mTc-MIBI and their myocardial uptake (MU) to determine MU of these tracers in NIT and IT assuming various degrees of vasodilatations in NIT and corresponding vasodilatations in IT, depending on CAS severity. The relative perfusion deficits (RPDs) defined as the ratios of MU in IT vs. NIT were determined under the different assumptions.

Results The table below lists the RPDs assuming mild CAS (~70% stenosis) resulting in CBF increase in IT amounting to 60% of that in NIT, moderate CAS (~ 80% stenosis, CBF increase in IT= 50% of that in NIT) and severe CAS (> 90% stenosis) with no increase in CBF above baseline, calculated with various levels of CBF increases in NITs. For mild/moderate CAS the greatest RPDs for both 201Tl and 99mTc-MIBI are associated with 2.0-fold increase in CBF. With 99mTc-MIBI, CBF increases of > 3.0 negate defect detection in the case of mild CAS and CBF increases of > 3.5 make it very difficult to detect even moderate CAS. As expected, 201Tl results in greater RPDs compared with 99mTc-MIBI, regardeless of CAS severity.

Conclusions Moderate CBF increases using regadenoson should result in more favorable RPDs with 201Tl and 99mTc-MIBI (and, expectedly, 99mTc-tetrofosmin) in patients with mild/moderate CAS. Since a lower dose of regadenoson of ~ 0.2 mg reportedly results in ~ 2.0-fold increase in CBF in NIT for > 2 minutes, it may be preferable to current dose of 0.4 mg and warrants further investigation