Incremental Prognostic Value of Subendocardial Myocardial Flow Reserve in Patients With Normal Perfusion
Abstract
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 median 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.
Article Details
Authors (38)
Diana M. Lopez
Cardiovascular 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.).
Jenifer M. Brown
Sanjay Divakaran
Daniel M. Huck
Brittany N. Weber
Cardiovascular 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.).
Jon Hainer
Cardiovascular 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.).
Sylvain Carre
Cardiovascular 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.).
Mark Lemley
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.).
Giselle Ramirez
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.).
Aakash Shanbhag
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.).
Paul Kavanagh
School of Chemistry and Chemical Engineering
Joanna X. Liang
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.).
Ron Blankstein
Cardiovascular 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.).
Sharmila Dorbala
Cardiovascular 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.).
Damini Dey
Stacey Knight
Viet T. Le
Intermountain Medical Center Heart Institute, Intermountain Healthcare, Murray, UT; Department of Internal Medicine, University of Utah, Salt Lake City, UT (S.K., V.T.L., S.M.).
Steve Mason
Intermountain Medical Center Heart Institute, Intermountain Healthcare, Murray, UT; Department of Internal Medicine, University of Utah, Salt Lake City, UT (S.K., V.T.L., S.M.).
Samuel Wopperer
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (S.W., P.C.).
Panithaya Chareonthaitawee
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (S.W., P.C.).
Thomas L. Rosamond
Department of Cardiovascular Medicine, The University of Kansas Medical Center, Kansas City, KS (T.L.R.).
Jacek Kwiecinski
Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland (J.K.).
Robert J.H. Miller
Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada (R.J.H.M.).
Leandro Slipczuk
Cardiology Division, Montefiore Health System/Albert Einstein College of Medicine, New York, NY (L.S.).
Mark I. Travin
Department of Radiology (Nuclear Medicine), Montefiore Einstein, Albert Einstein College of Medicine, Bronx, NY (M.I.T.).
Erick Alexanderson
Department of Nuclear Cardiology, Ignacio Chavez National Institute of Cardiology, Mexico City, Mexico (E.A., I.C.-J.).
Isabel Carvajal-Juarez
Department of Nuclear Cardiology, Ignacio Chavez National Institute of Cardiology, Mexico City, Mexico (E.A., I.C.-J.).
René R.S. Packard
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (R.R.S.P.).
Mouaz H. Al-Mallah
Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Academic Institute, Houston, TX (M.H.A.-M.).
Andrew J. Einstein
Attila Feher
Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT (A.F.).
Wanda Acampa
Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy (W.A.).
Rupa Sanghani
Section of Cardiology, Department of Medicine, Rush University Medical Center, Chicago, IL (R.S.).
Ronny R. Buechel
Robert A. deKemp
Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, ON, Canada (R.A.dK.).
Daniel S. Berman
Piotr J. Slomka
Marcelo F. Di Carli