AI-Derived Splenic Response in Cardiac PET Predicts Mortality: A Multi-Site Study.

Background: Inadequate pharmacologic stress may limit the diagnostic and prognostic accuracy of myocardial perfusion imaging (MPI). The splenic ratio (SR), a measure of stress adequacy, has emerged as a potential imaging biomarker.

Objectives: To evaluate the prognostic value of artificial intelligence (AI)-derived SR in a large multicenter Rb-PET cohort undergoing regadenoson stress testing.

Methods: We retrospectively analyzed 10,913 patients from three sites in the REFINE PET registry with clinically indicated MPI and linked clinical outcomes. SR was calculated using fully automated algorithms as the ratio of splenic uptake at stress versus rest. Patients were stratified by SR into high (≥90th percentile) and low (<90th percentile) groups. The primary outcome was major adverse cardiovascular events (MACE). Survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models adjusted for clinical and imaging covariates, including myocardial flow reserve (MFR ≥2 vs. <2).

Results: The cohort had a median age of 68 years, with 57% male patients. Common risk factors included hypertension (84%), dyslipidemia (76%), diabetes (33%), and prior coronary artery disease (31%). Median follow-up was 4.6 years. Patients with high SR (n=1,091) had an increased risk of MACE (HR 1.18, 95% CI 1.06-1.31, p=0.002). Among patients with preserved MFR (≥2; n=7,310), high SR remained independently associated with MACE (HR 1.44, 95% CI 1.24-1.67, p<0.0001).

Conclusions: Elevated AI-derived SR was independently associated with adverse cardiovascular outcomes, including among patients with preserved MFR. These findings support SR as a novel, automated imaging biomarker for risk stratification in Rb PET MPI.