Prognostic value of ¹⁵O-water PET global myocardial flow reserve: Proposed risk-based cutoffs

A global myocardial flow reserve (MFR) threshold of 2.5 is clinically used to define normal vasodilatory capacity with ¹⁵O-water positron emission tomography (PET) myocardial perfusion imaging but lacks prognostic validation. Since mean global MFR exceeds 3.5 in healthy individuals, the 2.5-3.5 range may represent an intermediate-risk "gray zone." We aimed to evaluate a 4-tiered global MFR categorization for risk stratification.

We retrospectively included patients with known or suspected chronic coronary syndromes who underwent clinically indicated ¹⁵O-water PET. Patients were stratified into four groups by global MFR: >3.5, 2.5-3.5, 1.5-<2.5, and <1.5. Major adverse cardiac events (MACEs) were defined as all-cause death or hospitalization for acute myocardial infarction, unstable angina, or acute heart failure. Prognostic value was evaluated using Cox hazard ratios (HRs; [95% confidence interval]).

Among 783 consecutive patients (median age: 68; 45% female), 129 MACEs occurred over a median follow-up of 3.5 years. Patients with an MFR >3.5 (n = 204) exhibited an annualized MACE rate of 0.6 per 100 person-years, with no MACE occurring during the first 2.5 years. An MFR of 2.5-3.5 (n = 310) had a 5-fold higher annualized MACE rate (3.1 per 100 person-years; HR: 5.4 [2.3-13]), increasing to 6.8 for an MFR measuring 1.5-<2.5 (n = 201; HR: 12 [5.1-28]) and 13.7 for an MFR <1.5 (n = 68; HR: 24 [10-59]). Group differences remained significant after multivariable adjustment (P ≤ 0.029).

Risk of MACE increases progressively with declining global MFR. We propose a 4-tiered categorization of MFR for reporting risk, using an MFR >3.5 to indicate a low-risk profile.