Differential association of heart rate response to regadenoson with death and heart failure hospitalizations according to ejection fraction in patients undergoing positron emission tomography myocardial perfusion imaging

Background Whether the prognostic value of heart rate responsiveness to pharmacological stress testing as assessed by stress or rest heart-rate ratio (HRR), adds prognostic value to contemporary PET MPI or varies according to ejection fraction (EF) has not been well-studied. Methods Consecutive patients undergoing Rb-82 positron emission tomography (PET) between 2019 and 2024 with regadenoson stress testing were included. The Andersen–Gill extension of the Cox model, which incorporates potentially recurrent events, was used to evaluate the association between HRR and the primary outcome, a composite of death or heart failure (HF) hospitalization. Univariable and multivariable models adjusted for clinical and PET-related variables were used. Restricted cubic splines were used to allow for nonlinearity. Interquartile hazard ratios (HRs) comparing the 75th (referent) vs the 25th percentiles of HRR were reported. Results Over a median follow-up of 553 days (IQR: 232 to 941 days), a total of 1,288 primary outcome events occurred among 7,808 patients. A greater HRR was associated with a lower incidence of the primary outcome in both the univariable (HR: 0.28; 95% CI: 0.23 to 0.36) and multivariable (HR: 0.60; 95% CI: 0.48 to 0.75) models. The association of HRR with the primary outcome was greater at higher EFs (P for interaction: .02), with HRs of 0.69, 0.55, 0.49, and 0.47 at EFs of 40%, 50%, 60%, and 70% respectively. Conclusions The prognostic value of HRR after pharmacological stress testing for death and HF hospitalization is most pronounced in patients with a preserved EF and is independent of traditional risk factors and PET parameters, including myocardial flow reserve.