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Updated: Jun 5, 2026
Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats
Published on: June 28, 2019
Incremental Prognostic Value of Subendocardial Myocardial Flow Reserve in Patients With Normal Perfusion
Diana M Lopez1, Jenifer M Brown, Sanjay Divakaran1
1Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women's Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.).
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 (MFRSE) beyond transmural MFR (MFRTM) 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 MFRSE 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 (MFRTM ≥2.0; MFRSE ≥2.1), discordant (low-MFRSE, normal MFRTM), and abnormal MFRTM. 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-MFRSE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFRTM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a median follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFRSE 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 MFRTM group.
Conclusions:
Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.
Insights
Reduced subendocardial myocardial flow reserve (MFR_SE) predicts adverse cardiovascular events, even with normal transmural MFR (MFR_TM). This finding refines risk stratification beyond traditional PET imaging metrics for better patient outcomes.
Area of Science:
- Cardiology
- Nuclear Medicine
- Medical Imaging
Background:
- Positron emission tomography (PET) myocardial flow reserve (MFR) is prognostic.
- Emerging data indicate reduced subendocardial flows predict adverse outcomes.
- The incremental value of subendocardial MFR (MFR_SE) over transmural MFR (MFR_TM) is unclear.
Purpose of the Study:
- To evaluate the incremental prognostic value of MFR_SE beyond MFR_TM.
- To assess risk stratification using MFR_SE in patients with normal MFR_TM.
Main Methods:
- Multicenter PET registry analysis of 6603 patients with normal perfusion.
- Exclusion criteria included prior bypass surgery, transplant, or low ejection fraction.
- Patients stratified into concordant-normal, discordant (low MFR_SE, normal MFR_TM), and abnormal MFR_TM groups.
- Major adverse cardiovascular events (MACE) and all-cause mortality compared across groups.
Main Results:
- Discordant low-MFR_SE patients were older and had more comorbidities.
- Compared to concordant-normal, discordant patients had higher MACE risk (HR 1.41) and mortality (HR 1.36).
- Discordant group showed intermediate MACE event rates (5.79%/year) versus normal (3.99%/year) and abnormal (8.35%/year) MFR_TM groups.
Conclusions:
- Subendocardial MFR (MFR_SE) identifies significant risk heterogeneity in patients with preserved transmural flow reserve.
- MFR_SE refines cardiovascular risk stratification beyond traditional PET metrics.
- This analysis supports the clinical utility of MFR_SE for improved risk assessment.
