Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron Emission Tomography.
BACKGROUND
Recent evidence suggests that the diagnostic accuracy of myocardial perfusion imaging is improved by quantifying stress myocardial blood flow (MBF) in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia positron emission tomography ((13)NH3-PET) diagnostic panel, including stress MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction with relative perfusion defect (PD) assessments to better detect functionally significant coronary artery stenosis.


RESULTS
A total of 130 patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET and invasive coronary angiography with fractional flow reserve (FFR) measurement. Diagnostic accuracy, optimal cut points, and discrimination indices of respective (13)NH3-PET quantitative measures were compared, with FFR as standard reference. The capacity to discern disease with stepwise addition of stress MBF, CFR, and RFR to qualitatively assessed relative PD was also gauged, using the category-free net reclassification index. All quantitative measures showed significant correlation with FFR (PET-derived CFR, r=0.388; stress MBF, r=0.496; and RFR, r=0.780; all P<0.001). Optimal respective cut points for FFR ≤0.8 and ≤0.75 were 1.99 and 1.84 mL/min per g for stress MBF and 2.12 and 2.00 for PET-derived CFR. Discrimination indices of quantitative measures that correlated with FFR ≤0.8 were all significantly higher than that of relative PD (area under the curve: 0.626, 0.730, 0.806, and 0.897 for relative PD, CFR, stress MBF, and RFR, respectively; overall comparison P<0.001). The capacity for functionally significant coronary stenosis was incrementally improved by the successive addition of CFR (net reclassification index=0.629), stress MBF (net reclassification index=0.950), and RFR (net reclassification index=1.253; all P<0.001) to relative PD.


CONCLUSIONS
Integrating quantitative (13)NH3-PET measures with qualitative myocardial perfusion assessment provides superior diagnostic accuracy and improves the capacity to detect functionally significant coronary artery stenosis.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01621438 and NCT01366404.
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Joo Myung
JM
Lee
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Chee Hae
CH
Kim
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.). bkkoo@snu.ac.kr larrycheon@gmail.com.
Bon-Kwon
BK
Koo
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Doyeon
D
Hwang
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Jonghanne
J
Park
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Jinlong
J
Zhang
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Yaliang
Y
Tong
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Ki-Hyun
KH
Jeon
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Ji-In
JI
Bang
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Minseok
M
Suh
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Jin Chul
JC
Paeng
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.). bkkoo@snu.ac.kr larrycheon@gmail.com.
Gi Jeong
GJ
Cheon
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Sang-Hoon
SH
Na
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Jung-Min
JM
Ahn
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Seung-Jung
SJ
Park
From the Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (J.M.L.); Department of Internal Medicine, Cardiovascular Center (C.H.K., B.-K.K., D.H., J.P., J.Z., Y.T., H.-S.K.), Department of Nuclear Medicine (J.-I.B., M.S., J.C.P., G.J.C.), and Department of Internal Medicine, Emergency Medical Center (S.-H.N.), Seoul National University Hospital, Korea; Institute of Aging, Seoul National University, Korea (B.-K.K., S.-H.N.); Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea (K.-H.J.); and Department of Cardiology, Heart Institute, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (J.-M.A., S.-J.P.).
Hyo-Soo
HS
Kim
D000368:Aged; D000641:Ammonia / Q000008:administration & dosage*; D019540:Area Under Curve; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D023921:Coronary Stenosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009590:Nitrogen Radioisotopes / Q000008:administration & dosage*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D015203:Reproducibility of Results; D056910:Republic of Korea; D012720:Severity of Illness Index
D009590:Nitrogen Radioisotopes; D019275:Radiopharmaceuticals; D000641:Ammonia
coronary artery disease; fractional flow reserve; myocardial ischemia; myocardial perfusion imaging; positron emission tomography