{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:01:42Z","timestamp":1790002902424,"version":"4.0.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n 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\n SE<\/jats:sub>\n ) beyond transmural MFR (MFR\n TM<\/jats:sub>\n ) remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n 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\n SE<\/jats:sub>\n cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction [MI], revascularization, or heart failure [HF] hospitalization) was determined using Youden\u2019s index. Patients were stratified into 3 groups: concordant-normal (MFR\n TM<\/jats:sub>\n \u22652.0; MFR\n SE<\/jats:sub>\n \u22652.1), discordant (low-MFR\n SE<\/jats:sub>\n , normal MFR\n TM<\/jats:sub>\n ), and abnormal MFR\n TM<\/jats:sub>\n . Clinical outcomes were compared by MFR groups.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3\u00b112.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFR\n SE<\/jats:sub>\n were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFR\n TM<\/jats:sub>\n 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-MFR\n SE<\/jats:sub>\n patients had a higher risk of MACE (hazard ratio [HR], 1.41; 95% CI, 1.22\u20131.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14\u20131.61) 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\u20136.49) compared with 3.99% (95% CI, 3.67\u20134.30;\n P<\/jats:italic>\n <0.001) in the concordant-normal group and 8.35% (95% CI, 7.71\u20139.00;\n P<\/jats:italic>\n <0.001) in the abnormal MFR\n TM<\/jats:sub>\n group.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.125.078816","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:00:20Z","timestamp":1780563620000},"page":"212-222","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Incremental Prognostic Value of Subendocardial Myocardial Flow Reserve in Patients With Normal Perfusion"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-9625","authenticated-orcid":true,"given":"Diana M.","family":"Lopez","sequence":"first","affiliation":[{"name":"Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-639X","authenticated-orcid":true,"given":"Jenifer M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0598-6502","authenticated-orcid":true,"given":"Sanjay","family":"Divakaran","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4221-8078","authenticated-orcid":true,"given":"Daniel M.","family":"Huck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-2091","authenticated-orcid":true,"given":"Brittany N.","family":"Weber","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-912X","authenticated-orcid":true,"given":"Jon","family":"Hainer","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Carre","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Program, Departments of Radiology and Medicine, Brigham and Women\u2019s Hospital, Boston, MA (D.M.L., B.N.W., J.H., S.C., R.B., S.D., M.F.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-880X","authenticated-orcid":true,"given":"Mark","family":"Lemley","sequence":"additional","affiliation":[{"name":"Artificial Intelligence in Medicine Research Center, Departments of Biomedical Sciences, Medicine, and Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA (M.L., G.R., A.S., P.K., J.X.L., D.D., D.S.B., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3730-5075","authenticated-orcid":true,"given":"Giselle","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Artificial Intelligence in Medicine Research Center, Departments of Biomedical Sciences, Medicine, and Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA (M.L., G.R., A.S., P.K., J.X.L., D.D., D.S.B., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-3071","authenticated-orcid":true,"given":"Aakash","family":"Shanbhag","sequence":"additional","affiliation":[{"name":"Artificial Intelligence in Medicine Research Center, Departments of Biomedical Sciences, Medicine, and Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA (M.L., G.R., A.S., P.K., J.X.L., D.D., D.S.B., P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2242-1936","authenticated-orcid":true,"given":"Paul","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Artificial Intelligence in Medicine Research Center, Departments of Biomedical Sciences, Medicine, and Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA (M.L., 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