Discordant low subendocardial myocardial flow reserve was associated with a higher risk of MACE compared to concordant-normal patients (HR 1.41; 95% CI 1.22-1.64).
Cohort (n=6,603)
Yes
Does discordant low subendocardial myocardial flow reserve predict increased risk of MACE in patients with normal perfusion on PET?
Subendocardial myocardial flow reserve provides incremental prognostic value for MACE and mortality in patients with normal perfusion and preserved transmural flow reserve.
Hazard Ratio: 1.41 (95% CI 1.22–1.64)
Absolute Event Rate: 5.79% vs 3.99%
p-value: p=<0.001
BACKGROUND: Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFR SE ) beyond transmural MFR (MFR TM ) remains unclear. METHODS: We studied patients in a multicenter PET registry with normal perfusion on stress/rest Rb-82 PET, excluding those with a previous history of coronary artery bypass surgery, heart transplantation, or left ventricular ejection fraction <40%. The optimal MFR SE cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction MI, revascularization, or heart failure HF hospitalization) was determined using Youden’s index. Patients were stratified into 3 groups: concordant-normal (MFR TM ≥2.0; MFR SE ≥2.1), discordant (low-MFR SE , normal MFR TM ), and abnormal MFR TM . Clinical outcomes were compared by MFR groups. RESULTS: Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3±12.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFR SE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFR TM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a m edian follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFR SE patients had a higher risk of MACE (hazard ratio HR, 1.41; 95% CI, 1.22–1.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14–1.61) compared with concordant-normal patients. The discordant group had an intermediate absolute risk of MACE, with an adjusted annualized event rate of 5.79% (95% CI, 5.10–6.49) compared with 3.99% (95% CI, 3.67–4.30; P <0.001) in the concordant-normal group and 8.35% (95% CI, 7.71–9.00; P <0.001) in the abnormal MFR TM group. CONCLUSIONS: Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.
Lopez et al. (2026) conducted a cohort in Normal perfusion on stress/rest Rb-82 PET (n=6,603). Discordant low subendocardial myocardial flow reserve (low-MFR SE, normal MFR TM) vs. Concordant-normal (MFR TM ≥2.0; MFR SE ≥2.1) was evaluated on Major adverse cardiovascular events (MACEs; death, myocardial infarction, revascularization, or heart failure hospitalization) (HR 1.41, 95% CI 1.22-1.64, p=<0.001). Discordant low subendocardial myocardial flow reserve was associated with a higher risk of MACE compared to concordant-normal patients (HR 1.41; 95% CI 1.22-1.64).