Incremental Prognostic Value of Regional Myocardial Flow Reserve Beyond Global Flow and Perfusion: REFINE PET

Background: The incremental prognostic value of regional myocardial flow reserve (MFR) assessed by positron emission tomography (PET) myocardial perfusion imaging (MPI) beyond global MFR remains unclear. We sought to evaluate the prognostic value of regional MFR in the international multicenter REFINE PET registry. Methods: This retrospective multicenter cohort study included 35,391 patients from 13 sites in the international REFINE PET registry who underwent rubidium-82 (82Rb) and 13N-ammonia(13NH3) PET MPI. Abnormal MFR was defined as <2.0. Patients were classified into three groups: MFR-Group 1 (normal global and regional MFR; n=19,744), MFR-Group 2 (normal global MFR but abnormal regional MFR; n=3,184), and MFR-Group 3 (abnormal global and regional MFR; n=12,463). Major adverse cardiovascular events (MACE) included all-cause mortality, non-fatal myocardial infarction, late revascularization (>90 days), and hospital admission for unstable angina. Results: During a mean follow-up of 4.0 ± 2.9 years, 9,903 patients (28.0%) experienced MACE. Annualized MACE rates increased stepwise across MFR-Groups 1-3 (4.0%/year, 7.5%/year, and 11.8%/year, respectively; p<0.001). Abnormal regional MFR independently predicted MACE after adjustment for clinical risk factors, global MFR, and stress total perfusion deficit (HR 1.34, 95% CI 1.25—1.43). Adding regional MFR to a model including global MFR significantly improved model fit (χ^2 4,784 to 4,871; p<0.001), discrimination (AUC 0.710 to 0.729; p<0.001), and reclassification (NRI 41.9%). Among patients with normal perfusion and preserved global MFR, abnormal regional MFR identified higher risk (5.0%/year vs. 2.8%/year; p<0.001). Conclusions: Regional MFR provided incremental prognostic value beyond conventional PET MPI findings, including global MFR, and may refine risk stratification, particularly when global MFR is preserved.