Prediction of All-Cause Mortality, Cardiovascular Mortality, and Angiographic Coronary Disease From LVEF Reserve: Findings From the Multicenter REFINE PET Registry

BACKGROUND: Left ventricular ejection fraction reserve (LVEF-R), defined as stress EF minus rest EF, is a marker for high-risk coronary artery disease in patients undergoing positron emission tomography myocardial perfusion imaging, but its prognostic and diagnostic significance in large real-world populations remains incompletely defined. We aimed to analyze the association of LVEF-R with mortality and high-risk obstructive coronary artery disease in a large multicenter cohort. METHODS: We analyzed 34 976 patients from 13 sites who underwent gated rest and vasodilator stress positron emission tomography myocardial perfusion imaging from the Registry of Flow and Perfusion Imaging for Artificial Intelligence with PET. Associations between LVEF-R and all-cause mortality and cardiovascular death were assessed using multivariable Cox regression models. In a subset with invasive coronary angiography (n=6843), the relationship between LVEF-R and angiographic disease was evaluated. RESULTS: A total of 9392 (26.9%) patients had an LVEF-R<0%. Over a median follow-up of 4.1 years, lower LVEF-R demonstrated a graded association with higher mortality. Compared with LVEF-R>5%, adjusted hazard ratios for all-cause mortality were 1.20 for LVEF-R 0% to 5% ([95% CI, 1.13–1.28]; P <0.001), 1.32 for −5% to 0% ([95% CI, 1.23–1.42]; P <0.001), and 1.38 for ≤−5% ([95% CI, 1.24–1.52]; P <0.001). A negative LVEF-R was also associated with high-risk coronary artery disease, including left main and 3-vessel disease. CONCLUSIONS: LVEF-R is an independent predictor of mortality, with a graded association between impaired reserve and adverse outcomes. A negative LVEF-R identifies patients with a higher likelihood of multivessel or left-main coronary artery disease, supporting its role as a clinically relevant marker of high-risk disease.